神经干细胞治疗：可持续治疗阿尔茨海默症的潜力和实用性

B3 4050

University of Pittsburgh, Swanson School of Engineering 2014-04-03 1

NEURAL STEM CELL THERAPY: THE POTENTIAL AND PRACTICALITY FOR SUSTAINABLY TREATING ALZHEIMER’S DISEASE

Jessie Liu (jrl99@https://www.wendangku.net/doc/9a13106531.html,, Bursic 2:00), Kelly Larson (krl46@https://www.wendangku.net/doc/9a13106531.html,, Budny 10:00)

Abstract—With the aging of the baby boomer generation, the demand for treatments for late-onset neurodegenerative diseases like Alzheimer’s Disease (AD) is rapidly increasing. Scientists have recently shifted their focus to neural stem cell therapy, which is proving to have great potential [1]. For this potential to be meaningful, the sustainability of the therapy must also be demonstrated. To show the practicality of neural stem cell therapy in the treatment of AD, the sustainability of the therapy, in terms of the improvement of quality of life, will be supported throughout the paper. Furthermore, in order to treat AD with stem cell therapy, adult neural stem cells must be selectively differentiated in relevant areas of the brain to induce neurogenesis and compensate for cell death caused by disease [2]. Nevertheless, issues in controlling differentiation along with ethical concerns have challenged the application of this treatment [3][4]. However, recent technology and research have mitigated some of these concerns and challenges and present neural stem cell therapy as a practical treatment for AD [2]. A background of the characteristics of AD will be given and several stem cell types will be discussed with regard to each type’s dis tinguishing characteristics and potential for therapy. This paper will use supporting evidence from various clinical trials and research articles to demonstrate that stem cell therapy is a viable alternative to the conventional and available treatments for AD. Opposition to this treatment will be detailed and appropriately countered. With advancements in controlling differentiation, stem cell therapy truly has the potential to sustainably meet the demand for treatment of Alzheimer’s disease.

Key Words—Al zheimer’s Disease, Cell Therapy, Differentiation, Neural Stem Cells, Neurogenesis, Regenerative Medicine, Sustainability

INTRODUCTION: THE DEMAND FOR EFFECTIVE AND SUSTAINABLE

TREATMENTS OF ALZHEIMER’S

DISEASE

Affecting as many as 5.1 million Americans over the age of 60, A lzheimer’s D isease is “an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry o ut the simplest tasks”

[5]. As this disease greatly affects populations worldwide, neural stem cell therapy is a worthwhile route toward providing effective treatments and should be further developed.

Before describing possibilities in treating AD, it is necessary to explain what AD is and why finding a treatment is so essential. AD involves neurodegeneration in the brain that may begin well before patients present symptoms. Mild memory impairment is typically one of the earliest symptoms of AD. As the disease progresses, memory loss becomes more severe, and other symptoms surface. Inability to learn new things, carry out tasks that require multiple steps, and increasing feelings of paranoia are all symptomatic of the later stages of AD [5]. Besides the physical symptoms, AD has many emotional effects on the patient and the family of the patient. As AD progresses into the later stages, patients may not only lose memories, but lose the ability to identify loved ones, or even themselves. These emotional and physical symptoms of AD along with the large population that it currently affects demonstrate the necessity of finding viable treatments.

However, in order for neural stem cell treatment to be practical, the sustainability of the innovation must be evaluated. “Sustainability” is a broad term that can be considered to have a multitude of definitions. In many cases, the term sustainable may be used to describe the ability of an innovation to have little negative impact on the environment. For the purposes of this paper, sustainability will be defined using a more unconventional definition: effectively meeting today’s needs, while considering how actions will impact the ability of meeting the needs of future generations. In this discussion of neural stem cells for AD, it is necessary to consider the ability of stem cell treatments to actively enhance the quality of life both now and in the future. To demonstrate the sustainability of neural stem cell therapy, finances, resources, and ethics will be considered throughout this paper.

Following a technical introduction and biological description of AD, stem cells as related to AD treatment and the biological stages of AD will be detailed. The difficulty of controlling neural stem cell differentiation for treatments will be acknowledged and discussed. Essential to any treatment consideration, case studies will be examined to corroborate the practicality of neural stem cell treatments.

Before the discussion of neural stem cell therapy, it is crucial to understand the biology of AD, so that the abilities of neural stem cell therapy to treat this disease may be explained.

NEUROGENESIS IN A LZHEIMER’S DISEASE: INDICATORS AND CURRENT

TREATMENTS

Named after Dr. Alois Alzheimer, Alzheimer’s disease has been recognized since 1906 when Alzheimer noticed changes in the brain tissue of a patient who was experiencing “memory loss, language problems, and unpredictable behavior” [5]. These changes in brain tissue he discovered (abnormal clumps and tangled bundles of fibers) are now known as amyloid plaques and neurofibrillary tangles, and are characteristic of AD [5]. These plaques and tangles, along with the loss of nerve connections, are the main features of AD, and will be further detailed along with physical symptoms and current treatments in the subsequent sections.

Biological Descriptors

Understanding how to control the loss of neurons and synaptic connectivity is necessary in order to find treatments of AD [6]. The accumulation of the toxic species of the β-amyloid (Aβ) peptide has been hypothesized as one of the main factors that lead to plaques and tangles, neurodegeneration, and changes in cognition [6][7]. Furthermore, the accumulation of the Aβ peptide interrupts healthy, normal brain functioning by disrupting the NMDAR (N-methyl D-aspartate receptors) ion channels, and destabilizing calcium equilibrium and energy metabolism [7].

Available Treatments

There is a large demand for finding treatments for AD, but currently available treatments are not meeting this demand. Most available drugs to improve AD target Acetylcholinesterase due to the cholinergic deficit (lack of acetylcholine) that is caused by AD [8]. Acetylcholine is a key neurotransmitter associated with the ability to pay attention. Decreases in Acetylcholinesterase have also been found to correlate with increases in neurofibrillary tangles and decreasing brain functioning [9]. It may seem as though drugs aiming to increase Acetylcholinesterase are the answer to AD, but these drugs do not provide a cure, and are beneficial strictly on a short-term basis. These drugs have been found to alleviate symptoms, but not prevent further neurodegeneration [7]. The lack of long-term treatments makes neural stem cell therapy a method worth investigating. Before detailing how neural stem cells would treat AD, it is fundamental to explain the technical aspects of stem cells.

SYNOPSIS: STEM CELLS

Whether it be neural cells, epithelial cells or mesenchymal cells, all cells begin as stem cells. As an “undifferentiated” form of their later counterparts, stem cells are potent, meaning that they have the ability to turn into other types of potential cells. Differentiation is the process by which stem cells are influenced by their surroundings, including both external and internal factors, causing them to progress from one stage to another. T hese “stages” are s mall changes that direct stem cells in the path of a certain type of cell [3].

Types of Stem Cells

There are four main types of stem cells, embryonic, fetal, adult, and iPS [10]. Only in the pure embryo state do stem cells possess the total pluripotent (meaning the ability to differentiate into any type of cell) potential, while adult stem cells are partially differentiated embryonic stem cells. For example, neural adult stem cells have the potential to differentiate into the various types of cells that make up the nervous system.

Ethical oppositions may hinder the ability to further develop this treatment, thus it is imperative to consider the ethical sustainability of neural stem cell treatment in improving the quality of life in AD patients. With embryonic stem cells, extraction of the cells from embryos is instrumental in performing research. This process and its effects garner controversy, however, revolving around when human life begins since extraction ends the potential of the embryo to further develop. Questions mainly arise from certain religious and political affiliations, most notably Christianity and Republican conservatism, respectively [4]. For the purpose of treating Alzheimer’s disease, embryonic stem cells can be used but are not necessary, showing that neural stem cell therapy has low probable cause of encountering social resistance. This further promotes neural stem cell therapy as ethically sustainable and a practical treatment for neurodegenerative diseases. As such, adult stem cells will be focused upon.

Contrary to embryonic stem cells, adult stem cells can be extracted from adult humans without these effects on human life. Although on a very large and general scale adult stem cells can then be said to have little controversy, ethical issues do exist for them [11]. These issues do not surround the actual extraction of adult stem cells or use of them in research but rather their implementation in challenging human identity. Concerns arise regarding the commercialization of stem cells and whether or not this challenges the concept of human dignity [12]. Just like with the ethical and moral issues surrounding embryonic identity, these concerns depend on one’s definition of hum an identity. If the definition only defines human identity as the human together as a whole, then little issues arise. However, if one defines human identity as encompassing everything human—even a human cell that is not a human by itself—then adult human stem cell commercialization and patents are ethically unsound [12]. By this definition, the use of any cell in medical research could be considered unethical, potentially hindering further medical

development. As this is not the case and cells are currently used in medical research, the use of neural stem cells for the treatment of AD is sustainable from an ethical standpoint.

Adult stem cells are multipotent, meaning that they can proliferate more of their phenotype as well as differentiate into more than one type of cell. Adult stem cells include bone marrow-derived hematopoietic, mesenchymal, and umbilical cord. Mesenchymal stem cells (MSCs) are extracted from fat, bone marrow, or placenta, while umbilical cord stem cells are extracted from a newbo rn’s placenta and umbilical cord [10]. In the treatment of AD, these different types of adult stem cells could potentially be isolated and differentiated into neural stem cells. However, there are limitations to this process.

Technical problems arise with adult stem cells specifically regarding their potency (ability to differentiate into different cells) [10]. Certain types of adult stem cells are far less likely to differentiate into one type of cell than another. Dr. Paul Knoepfler, an Associate Professor of the Department of Cell Biology and Human Anatomy at the University of California Davis’ Medical School, explains the unlikelihood of muscle-derived adult cells to differentiate into neural cells in his book “Stem Cells: An Insider’s Guide.” There fore, there are limitations in the types of adult stem cells that may differentiate into neural cells to treat Alzheimer’s disease. The difficulty of controlling differentiation is one of the main challenges in stem cell treatment, yet is necessary in order for its success.

iPS cells, induced-pluripotent stem cells, are essentially non-stem cells that are “induced” into becoming stem cells and are virtually undistinguishable from embryonic stem cells [10]. For instance, iPS cells have been made from fibroblasts by overexposing them to transcription factors. Once a cell is induced into being a pluripotent stem cell, it has the ability to differentiate into virtually any type of cell. Furthermore, iPS cells can be made from a patient’s own skin, thereby re ducing the chances of the body rejecting the stem cells [10]. In terms of AD, this means that a patient could potentially receive neural stem cell therapy from neural iPS cells that have been extracted from their own skin.

Some disadvantages to iPS cells can be hypothesized but have not yet been proven, such as the possibility of mutations in iPS cells as they replicate [10]. However, concrete disadvantages to iPS cells, such as the necessary time and cost, are more obvious. When analyzing the sustainability of neural stem cell treatment for AD, time and cost factors must be taken into account, as inefficiency in these factors could hinder the development of treatments for the disease. iPS cells take approximately six months to produce and validate, and cost estimates “range as high as tens of thousand dollars per clinical grade human iPS cell line” [10]. Methods for overcoming these cost barriers have been introduced. One such idea includes creating an iPS cell bank that would serve as a more cost-efficient alternative to individually isolating cells from patients to be used on themselves [10]. By decreasing the time and money needed to have patients receive neural stem cell treatment, the potential for this therapy to promote the quality of life in AD patients increases.

Whether it be iPS, adult, or any other type of stem cell, the key issue is controlling differentiation. Research in this area has increased the potential to successfully use stem cells in order to improve the quality of life of individuals with AD.

CONTROLLING DIFFERENTIATION

Controlling differentiation is at the core of stem cell treatment research. When culturing stem cells for research, there can be great difficulty with exploiting differentiation and combating the high natural frequency of proliferation. While proliferation is simply generating more cells, differentiation is the process of stem cells becoming specific phenotypes of cells [3]. Most treatment ideas stem from the concept of regenerating lost cell tissue and for any of these ideas to be plausible, proliferation versus differentiation of stem cells must be controlled in order to exploit the potential and yield the desired type of cells. In the case of neural stem cell therapy for AD treatment, lost neural tissue cells are regenerated by inducing neurogenesis. Here is where researchers have difficulty moving forward. For neural stem cells, since its applications are relatively new, differentiation has not been studied as much as other stem cells, such as cardiac stem cells.

Differentiation is typically governed by three types of microenvironmental cues—soluble signals, cell-cell interactions, and insoluble signals [13]. Soluble signals have been thoroughly researched, but difficulties arise in studying the other two cues. In particular, cell-cell interactions and their role in differentiation have been widely studied with most adult stem cells, but not with neural stem cells. More unconventional methods like the nature of the growth substrate and epigenetic regulation have also been introduced [13].

Soluble Signals

Although much can be learned from in vitro (not in life) experiments, it is important to take in vivo(in life) microenvironmental interactions into account in addressing attempts to control differentiation [3]. One such interaction is that of soluble signals. This is perhaps one of the most easily apparent factors of differentiation as it is simple to imagine adding, for example, a solution to a substance and having a change take place. As soluble signals have been widely and extensively researched there are many different soluble signals studied.

A major growth factor pathway includes basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). During early development, cells begin by responding mainly to bFGF and later shift to respond mainly to EGF [3]. bFGF

serves to promote neural stem cell proliferation at early stages, while EGF takes over this task in later stages when responsiveness to this factor increases [3]. In addition, other factors like insulin and insulin-like growth factor (IGF) promote proliferation by cooperating with EGF signaling [3]. Together, these three factors—while promoting proliferation—serve to regulate the proliferation by controlling cell numbers [3].

Although these factors can control and promote proliferation—and are used frequently in differentiation experiments—they do little in promoting differentiation of the cells. Transforming growth factor (TGF)-αalso promotes proliferation [3]. However, TGF-β can have anti-proliferative effects while having pro-differentiating effects on the cells [3]. As a result TGF-β can promote neuronal survival after strokes and promote neurogenesis. A member of this TGF-β factor family is glial-derived neurotrophic factor (GDNF). This factor has similarly been shown to promote neurogenesis as well as differentiation of neural progenitor cells. An over expression of GDNF activates the genes related to the differentiation of neural progenitor cells [3].

In vitro, the use of bFGF and EGF can be used to model the naturally occurring in vivo proliferation process. Furthermore, they can both be used in several combinations with other factors to attempt to yield the correct phenotype of cells. However, problems can occur if one factor lessens the effects of another. Without the factors working in harmony, the resulting cells may have little of the desired yield. The previously mentioned TGF-β is an example of a factor acting as an antagonist to other factors, like bFGF and EGF, by discouraging proliferation, but also inducing the desired differentiation. Although the effects of many growth factors have been studied, it is not enough alone to control differentiation. In vivo, soluble factors are not the only aspect of differentiation. Thus, looking at soluble factors singularly is not practical but can provide a foundation to build upon in order to gain sufficient control over differentiation [3].

Role of the Extracellular Matrix

Whether it is in vitro or in vivo, stem cell niches are essential for the development of differentiating cells. These niches are microenvironments that sustain proliferation, protect the regenerative capacities of the stem cells, and in vivo contain various membranes. While these membranes serve as a structure for the cells to adhere to, they also ensure growth control and appropriate cell polarization and orientation. Part of this cell niche is the extracellular matrix (ECM). Interactions between the cell and the ECM are imperative in the cells’ behavior and function. As such, the ECM provides important cues for proliferation, differentiation, and regenerative neurogenesis [3].

Proteins within the ECM play a role similar to soluble signaling factors. For example, epidermal growth factor receptor (EGFR) interacts and responds to bFGF and EGF, each at their respective times in development. As one might imagine, EGFR helps promote proliferation by responding to these soluble signals. The ECM is also capable of trapping growth factors—such as bFGF and EGF—allowing the ECM to play a role in regulating and maintaining different concentrations of growth factors [3].

Not only does the ECM interact with growth factor signals, but the protein patterns within the ECM have their own effect on neuronal and glial differentiation. This effect suggests that neural stem cells can perhaps undergo differentiation by simply sensing the difference in the protein patterns of the ECM as it develops [13].

In one experiment, an ECM protein, laminin, was patterned in squares, stripes, and grids on a surface. Cell adhesion and growth only occurred on these patterned regions and occurred best with laminin as opposed to other ECM proteins like fibronectin and collagen. Rat hippocampal neural stem cells were used and were first treated with bFGF to promote cell proliferation. Withdrawing bFGF from the medium allowed for proliferation to be stopped and differentiation to be initiated. As shown in Figure 1 section A, these cells were then cultured on the laminin squares, stripes, and grids in varying dimensional sizes. The results showed decreased neuronal differentiation on the squares as opposed to the stripes that had one way cell-cell interactions, immediately suggesting the importance of cell-cell interactions as well as the ECM patterns [13].

FIGURE 1 [13]

Diagram of ECM protein patterns experiment showing the increased neuronal differentiation on grid patterns.

Furthermore, there was increased neuronal and decreased glial differentiation observed on the grid patterns of laminin, as show in section C and D of Figure 1. These grid patterns had been designed to increase cell-cell interactions and

the

results corroborate that cell-cell interactions are just as important as ECM protein patterns.

Besides its interactions with cells and soluble signals, the ECM provides a support system and structure for which the cells to adhere. Without such a system, the cells would hardly differentiate together, resulting in cells finding their way into other tissues. This would further prevent the intended treatment from taking place. However, implementing ECM techniques, some control can be gained over differentiation.

The Nature of the Growth Substrate As the ECM provides a structure for adhesion, proliferation, and differentiation, the ECM is a type of growth substrate. Considering the ECM in this light as well as the importance of stem cell niches, the nature of the growth substrate becomes an important factor in succeeding to exploit differentiation.

One such growth substrate is poly(lactic-co-glycolic acid) (PLGA) microfibers. Before this method was developed, fibrous substrates for neural stem cells had not been investigated to a great extent. However, if used as a growth substrate, these microfibers can induce linear alignment of neuronal differentiated stem cells [14]. Originally the cells were in random alignments on the fibers, but after twenty days only the cells that expressed neuronal proteins were aligned along the fibers [14]. Differing from other substrate approaches, such as the ECM protein patterns previously discussed, this method gives a new type of physical evidence of differentiation to be observed.

Another growth substrate to show potential for controlling differentiation is graphene. Graphene has been quite popular in modern day technology as it possesses properties like electric conductivity and transparency, but it has not previously been considered as a growth substrate [15]. Recently, however, graphene has proven to be a beneficial growth substrate in several respects. Similarly to the PLGA microfiber method, differentiation is initiated by removing bFGF and EGF from the cells before moving them to the graphene. The graphene was also coated with laminins prior to the cells being cultured. During this experiment, differentiation of cells on graphene was compared to that on glass. Though at first there seemed to be little difference, after three weeks there were more differentiated neuron cells on the grapheme than on the glass [15]. After one month, both materials had cells completely differentiated into neurons. However, the cells on the glass were clustered and often detached from the glass, causing a smaller amount of viable cells in the end. In Figure 2, notice the abundance of neuronal differentiated cells on graphene as opposed to the small and clustered amounts of mainly glial differentiated cells on glass. After further analysis, it was found that overall the graphene promoted cell adhesion as well as a more favorable microenvironment for the cells [15].

FIGURE 2 [15]

Images of the immunostained cells on glass and graphene with GFAP in red indicating glial differentiated cells, Tuj1 in green indicating neuronal differentiated cells, and DAPI in blue indicating every cell nucleus.

In this experiment alone, several differentiation techniques are used. The traditional use of soluble signals, namely bFGF and EGF, to initiate differentiation and the use of laminins from the ECM to simulate an in vivo environment combined with the unconventional growth substrate proved beneficial. However, the nature of the growth substrate does not depend alone on the actual material but also the shape of such substrates.

Nanotopographical manipulation, a method of altering the growth substrate, has also been shown to promote differentiation and focal adhesion. Focal adhesion causes cytoskeleton reorganization which ultimately can alter gene expression and cause differentiation. Similar methods have proved effective in the differentiation of human mesenchymal, human embryonic, and human neural stem cells [16]. This study showed that there was enhanced differentiation and focal adhesion on grooved and pillared surfaces [16]. These results clearly demonstrate the potential of nanotopographical manipulation as a method for enhancing differentiation in hand with traditional methods that result in biochemical and biophysical cues.

Epigenetic Regulation

Another unconventional method being studied to control differentiation is the use of epigenetic regulation. “Epigenetic” simply refers to heritable influences that do not come with a change in the DNA sequence. Proper activation and deactivation of specific genes is crucial in each step of neural stem cell differentiation.

Found to play a part in astrocyte formation, DNA methylation is a major epigenetic mechanism that controls a vast amount of cellular events [17]. DNA methylation controls gene expression by methylation of specific nucleotides that then interfere with the binding of transcription factors to their target sequences [17]. Another process is to have a different protein bind to the nucleotides that have been methylated which, in turn, directly suppresses gene expression [17]. In order to produce astrocytes in mice, glial fibrillary acidic protein (GFAP) is hypermethylated and only demethylated once the cell is in a lineage to become an astrocyte [17]. Possible exploitation of methods like these would be ideal for further controlling differentiation. Unfortunately, not much is known about the actual specific mechanisms behind them.

In comparison to DNA methylation, histone modification is much more diverse and complex. Two of the core histones, H3 and H4, have long amino tails that can undergo several modifications including methylation. Depending on what is methylated, gene expression in the stem cells can be activated or deactivated [17]. Just like the DNA methylation, these effects can be vast and widespread.

Noncoding RNA also has effects in neural stem cell differentiation. MicroRNA (miRNA) has been extensively studied as taking part in the fate of neural stem cells [17]. miRNA is RNA that can bind to target mRNAs and repress their translation and stability to alter gene expression. miR-124a has specifically been shown to participate in in vitro stem cell differentiation into neurons. This type of miRNA is regulated by neuron restricted silencing factor/RE-1 silencing transcription factor (NRSF/REST), which is only present in neural stem cells. As such, differentiation into neurons is typically not stable. Without NRSF/REST, however, miR-124a expression is upregulated producing a preference for neuronal lineage differentiation [17].

Epigenetic regulation has been proven to play a role in stem cell differentiation by DNA methylation, histone modification, and the use of noncoding RNA. Exploitation of these methods could in turn produce lineages of cells that are purely neuronal, thus perfect for practical, sustainable treatments.

NEURAL STEM CELLS APPLIED TO

ALZHEIMER’S DISEASE

Now that the biology of AD, current available treatments of AD, types of stem cells, and concerns with differentiation have all been detailed, neural stem cells with specific regard to AD can be discussed. Once stem cells have been differentiated into neural stem cells, they can be used in the treatment of AD . Earlier, excess amounts of the β-amyloid (Aβ) peptide were described as one of the contributing factors to the symptoms of AD. In order to reduce the effects of this factor, neural stem cells can be introduced to various stages of the progression of AD.

As shown in Figure 3, the overproduction/decreased clearance of Aβ leads to a complex web of abnormalities including synaptic dysfunction and Aβ oligomers and plaques, which further drives for causing gliosis and inflammation and the characteristic (neurofibrillary) “tangles”.

FIGURE 3 [6]

The various stages that lead to cognitive impairment, and the areas in which neural stem cells may become

involved.

As a result, cognitive impairment is present in individuals due to synaptic and neuronal loss. However, by introducing neural stem cells and genetically-modified neural stem cells at various stages of this causal chain, the continuation of these various stages can be significantly reduced through neurogenesis to account for cell death or abnormalities [6].

Furthermore, Figure 4 shows how neural stem cells may physically be injected in the basal forebrain along with compounds or antibodies to restore endogenous neurogenesis in ventricles in AD brains.

FIGURE 4 [18]

The areas affected by AD can be injected with stem

cells.

The left side of the figure shows a healthy brain, while the right shows an AD brain. Notice the characteristic neurofibrillary tangles and “senile” (amyloid-β) plaques in the AD brain, and also that the AD brain is smaller, indicating neuronal death. Neurogenesis resulting from the addition of these stem cells along with the compounds or antibodies would potentially aid in restoring the AD brain to its original health, or at least halt further damage.

Theoretically, neural stem cells appear to have great potential for treating AD. Analysis of real case studies indicates that this theory is testable, practical, and within this generation’s reach.

Case Studies

One notable clinical trial includes the injection of iPS cells in twelve human Amyotrophic Lateral Sclerosis (ALS)—or Lou Gehrig’s disease—patients. In analysis of the trial, it was found that the progression of the disease did not accelerate in any subject [19]. The findings of the clinical trial provide much hope for iPS cells in treating AD, as one of the main contributors, Feldman, said herself that “Alzheimer’s is go ing to be easier to do than ALS,” [20]. She then further explained that having the brain as the target of stem cells (rather than the spinal cord as in ALS) allows for a greater number of stem cells to be injected, promising greater and faster benefits [20]. The success of this ALS trial gives good reasoning that iPS cells may be as successful in halting disease progression in AD as well.

Another study dealt directly with AD and iPS cells. The 2012 Nobel-Prize winner Shinya Yamanaka contributed to the online article “Anti-AβDrug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer’s Disease,” that discussed the findings of a study involving iPS cells and AD [21]. The results of the study found that anti-Aβdrug screening using iPS cells requires sufficient differentiation to become neural stem cells, further impressing the need to control differentiation.

NEURAL STEM CELL THERAPY: PROVIDING A REALISTIC TREATMENT FOR ALZHEIMER’S DISEASE

Looking towards the future, neural stem cell therapy may provide the means needed in order to find effective treatment—or even a cure—for Alzheimer’s disease. Previously mentioned studies have shown reasons to be hopeful for the success of neural stem cell treatment. Various new methods have shown the possibility of neural stem cell therapy to be a practical, and therefore sustainable, innovation. Potential paths to lower the cost and time needed for patients to receive treatment have made this therapy a worthwhile development. The necessity of discussing the sustainability of this treatment is to ensure that it has the ability to continue improving the quality of life in AD patients in the future. In order for the treatment to be successful over a long period of time, potential obstacles to the development of the therapy must be considered. Such hurdles include ethical oppositions and technical issues in controlling differentiation. The main ethical concerns with adult stem cells have been countered and new methods for controlling the differentiation of neural stem cells show great potential. Techniques combining several aspects of differentiation are proving most productive. Bringing soluble signals together with ECM protein patterns, in vivo microenvironmental qualities, and unconventional growth substrates has been demonstrated to aid in not only controlling but also understanding differentiation to a further extent. Despite these advancements, the demand for more steps to be taken in neural stem cell research is key to ensuring that AD patients can receive the full benefits of neural stem cells. Neural stem cell therapy has immense potential to replace current Alzheimer’s disease medications, providing the opportunity for long-term treatments or cures for those suffering from Alzheimer’s disease.

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[20] R. Beene. (2014). “UM Researcher to Test Stem Cell Treatment for Alzheimer’s.” Neualstem, Inc. (Online Article). https://www.wendangku.net/doc/9a13106531.html,/neuralstem-in-the-news/75-um-researcher-to-test-stem-cell-treatment-for-alzheimers [21] N. Yahata, M. Asai, S. Kitaoka. (2011). “Anti-Aβ Drug Screening Platform Using Human iPS Cell-Derived Neurons for the Treatment of Alzheimer’s Disease.” PLOSone. (Online Article). DOI: 10.1371/journal.pone.0025788

ADDITIONAL SOURCES

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T. Arinzeh, Y. Lee. (2012). “The Influence of Piezoelectric Scaffolds on Neural Differentiation of Human Neural Stem/Progenitor.” Tissue Engineering. (Online Article). DOI: 10.1089/ten.tea.2011.0540

R. Ayala, D. Yang, C. Zhang, et al. (2011). “Engineering the cell-material interface for controlling stem cell adhesion, migration, and differentiation.” Biomaterials. (Online Article). DOI: 10.1016/j.biomaterials.2011.02.004

S. Banno, H. Inomata, L. Jakt, et al. (2011). “Intrinsic transition of embryonic stem cell differentiation into neural progenitors.” Nature. (Online Article). DOI: 10.1038/nature09726

L. Boyer. (2012). “Stem cell differentiation study probes genetic basis of heart disease.” Stem Cell Research News. (Online Article). https://www.wendangku.net/doc/9a13106531.html,/ps/i.do?action=interpret&id=GALE %7CA303449833&v=2.1&u=upitt_m

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M. Israel, S. Yuan, C. Bardy, et al. (2012). “Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.”Nature.(Online Article). DOI: 10.1038/nature10821

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J. Oh, L. Peterson, D. Sakaguchi, et al. (2011). “Amphiphilic Polyanhydride Films Promote Neural Stem Cell Adhesion and Differentiation.” Tissue Engineering. (Online Article). DOI: 10.1089/ten.tea.2011.0095

ACKNOWLEDGEMENTS

We would like to thank first and foremost Diane Kerr, our writing instructor, for guiding us along each step of this process. Help received from our co-chair, Abigail Slavinsky, and our session chair, Areej Sajjad, has also been instrumental. Furthermore, we thank Judy Brink for her guidance in our research. We would finally like to thank the Engineering Department for giving us this opportunity.

阿尔茨海默症康复治疗

阿尔茨海默病康复治疗 辛苦劳碌大半辈子，原应安享晚年，但是，由于被疾病困扰，很多老人在晚年时过得很不好。一方面，老人受到疾病折磨，痛苦不堪；另一方面，又觉得给子女造成了麻烦，心理负担重。在众多疾病中，阿尔茨海默病又是其中一种比较特殊的疾病。那么，接下来，小编就给您说说阿尔茨海默病康复治疗。 自2017年1月1日起，青岛市率先试点将重度失智老人纳入制度保障，试行“失智专区”管理，这也是岛城继身体失能老人享受护理保障待遇之后又一全国首创。为进一步扩大试点范围，近期，青岛市社保局在原来6家试点护理机构的基础上新增5家护理机构，并于2018年1月1日起正式开展业务，而新增设的单位中，青岛颐佳医养医疗管理有限公司市南颐佳诊所（颐佳老年公寓）是市南区一家试点单位。青岛户籍的重度失智老人入住颐佳“失智专区”可以享受医保报销了，这无疑对失智老人和家属来说是一个特大好消息。

省钱！市南区！入住老人可享医保报销 青岛市人社局、财政局去年联合出台了《关于将重度失智老人纳入长期护理保险保障范围并实行“失智专区”管理的试点意见》，决定将入住机构照护的重度失智老人试点纳入长期护理保险保障范围，在全国率先探索建立针对失智老人的精准护理保障制度。凡参加青岛市社会医疗保险，年满60周岁的参保职工和一档缴费成年居民，经社保经办机构确定的失智诊断评估机构特约专家明确诊断，其基本生活照料和与基本生活密切相关的医疗护理费用，由护理保险资金按规定支付。符合条件的失智老人在护理保险“失智专区”接受照护服务期间发生的符合规定的医疗护理费，参保职工报销90%，一档缴费成年居民报销80%。“颐佳是市南区家享受此类医保报销的养老机构，入住颐佳的失智老人达到要求的可以每个月享受近千元的报销比例，这将为失智老人

阿尔茨海默症

阿尔茨海默症 阿尔茨海默病(Alzheimer’s disease,AD)又称老年痴呆病，于1906年被德国医生Alois Alzheimer首次发现。它是一种慢性进行性神经退行性疾病，多发于60岁以上老年人，早期多表现为记忆障碍，以近期记忆力受损为主，随着病情的进展，病人可出现失语、失写、焦虑、淡漠、攻击行为以及日常生活不能自理等表现，严重影响病人的生活质量，给病人造成深重的痛苦，给家庭和社会带来沉重的负担。 临床表现： 该病起病缓慢或隐匿。多见于70岁以上（男性平均73岁，女性为75岁）老人，少数病人在躯体疾病、骨折或精神受到刺激后症状迅速明朗化。女性较男性多（女∶男为3∶1）。主要表现为认知功能下降、精神症状和行为障碍、日常生活能力的逐渐下降。根据认知能力和身体机能的恶化程度分成三个时期。 第一阶段（1～3年） 为轻痴呆期。表现为记忆减退，对近事遗忘突出；判断能力下降，病人不能对事件进行分析、思考、判断，难以处理复杂的问题；工作或家务劳动漫不经心，不能独立进行购物、经济事务等，社交困难；尽管仍能做些已熟悉的日常工作，但对新的事物却表现出茫然难解，情感淡漠，偶尔激惹，常有多疑；出现时间定向障碍，对所处的场所和人物能做出定向，对所处地理位置定向困难，复杂结构的视空间能力差；言语词汇少，命名困难。 第二阶段（2～10年） 为中度痴呆期。表现为远近记忆严重受损，简单结构的视空间能力下降，时间、地点定向障碍；在处理问题、辨别事物的相似点和差异点方面有严重损害；不能独立进行室外活动，在穿衣、个人卫生以及保持个人仪表方面需要帮助；计算不能；出现各种精神症状，可见失语、失用和失认；情感由淡漠变为急躁不安，常走动不停，可见尿失禁。 第三阶段（8～12年） 为重度痴呆期。患者已经完全依赖照护者，严重记忆力丧失，仅存片段的记忆；日常生活不能自理，大小便失禁，呈现缄默、肢体僵直，查体可见锥体束征阳性，有强握、摸索和吸吮等原始反射。最终昏迷，一般死于感染等并发症。 AD的发病机制： 2.1 β淀粉样蛋白学说即“Aβ假说”，目前该假说广为大家所接受。β淀粉样蛋白来源于中枢神经系统星形胶质细胞、神经元及内皮细胞等所表达的蛋白质的蛋白样淀粉前体。AD所具有的一个最典型的组织病理特征便是β淀粉样蛋白在中枢神经系统组成的斑块，即β淀粉样蛋白的异常沉积[2]。该假说认为，细胞外异常聚集的β淀粉样蛋白通过炎症反应、自由基反应等多种细胞级联反应，可通过不同途径作用于胶质细胞和神经元，最终致使神经元功能出现异常甚至死亡，进而引起认知障碍[3]。β淀粉样蛋白异常聚集多由环境及遗传因素作用引起，如生活方式的改变（如嗜酒、高脂高盐饮食、接触放射性、化学毒性物质等），从而导致β淀粉样蛋白的异常代谢[4]。尽管Aβ假说仍备受到争议，但目前他在AD研究领域的地位仍无可替代。 2.2 tau蛋白异常磷酸化学说AD的另一个标志性的病理特征是神经细胞内高度磷酸化tau蛋白异常聚集形成神经原纤维缠结[5]（neurofbrillary tangles，NFT）。Tau蛋白作为一种胞质蛋白，与微管蛋白有较高的亲和力，进而使神经元微管的结构保持稳定，并保证神经

阿尔茨海默病的非药物治疗

Advances in Clinical Medicine 临床医学进展, 2020, 10(4), 546-549 Published Online April 2020 in Hans. https://www.wendangku.net/doc/9a13106531.html,/journal/acm https://https://www.wendangku.net/doc/9a13106531.html,/10.12677/acm.2020.104085 Non Drug Treatment of Alzheimer’s Disease Yun Jin, Chunyu Zhang, Hu Rile Temur Inner Mongolia Medical University, Hohhot, Inner Mongolia Received: Mar. 28th, 2020; accepted: Apr. 13th, 2020; published: Apr. 20th, 2020 Abstract Alzheimer’s disease is an increasingly serious public health problem, accounting for more than two-thirds of dementia. Alzheimer’s disease is characterized by chronic progressive deterioration of cognitive function, often accompanied by psychopathology, including personality changes and social isolation, which seriously reduce the quality of life. At present, there is no feasible treat-ment or modern drugs for AD symptoms to slow or reverse the progression of AD or prevent the progression of neurodegeneration. With the in-depth study of Alzheimer’s disease, non-drug thera-py has formed a new way of intervention because of its advantages such as small side effects, easy acceptance by patients and their families. Keywords Alzheimer’s Disease, Non Drug Treatment, Delay Progress 阿尔茨海默病的非药物治疗 靳云，张春雨，呼日勒特木尔 内蒙古医科大学，内蒙古呼和浩特 收稿日期：2020年3月28日；录用日期：2020年4月13日；发布日期：2020年4月20日 摘要 阿尔茨海默病是日益严重的公共卫生问题，占痴呆人数的2/3以上。阿尔茨海默病的特点是认知功能的慢性进行性恶化，经常伴有精神病理状态，包括人格改变和社会孤立，这些症状严重降低了生活质量。 目前，没有一种可行的治疗AD症状的方法或现代药物能够减缓或逆转AD的进展或阻止神经退变的进展。 随着对阿尔茨海默病的深入研究，非药物治疗因其副作用小、患者及家属易接受等优点形成了一种新的干预思路。

阿尔茨海默症护理

（标题：宋体，四号。正文：宋体，小四。行间距1.5倍。级别符号按浙 大出版社编书规范） 阿尔茨海默症护理 阿尔茨海默症（Alzheimer disease，AD），又称老年性痴呆，是一种中枢神经系统变性病，起病隐袭，病程呈慢性进行性，是老年期痴呆最常见的一种类型。主要表现为渐进性记忆障碍、认知功能障碍、人格改变及语言障碍等神经精神症状，严重影响社交、职业与生活功能。 【护理评估】 1. 病史了解有无家族史、吸烟史，询问起病时间、治疗经过、病情控制情况以及有无精神刺激、感染及铝摄入过量等诱因。 2. 症状、体征 （1）轻度：语言功能受损，记忆减退，时间观念混淆，迷失方向，做事失去兴趣，出现忧郁或攻击行为。 （2）中度：日常生活无法独立完成，自理能力下降，出现幻觉或其他异常行为。 （3）重度：明显的语言理解和表达困难，不能辨认家人和熟悉的物品，行走困难，大小便失禁，完全卧床。 4. 辅助检查了解脑电图、CT及精神量表测试等结果。 5. 心理社会支持情况 【护理措施】 1. 按内科一般护理常规。 2. 饮食护理营养丰富、清淡可口的食物，以半流质或软食为宜，防误吸窒息睡 前禁饮浓茶、咖啡，吸烟。 3. 休息与活动室温适宜，环境安静，失眠者可给予小剂量安眠药。 4.预防感染做好基础护理，大小便失禁者及时更换衣物，保持皮肤清洁干燥， 预防压力性损伤，2h更换体位。

5. 心理护理对出现焦虑的患者安排有趣的活动，指导听舒缓的音乐。对表现出抑郁的患者，耐心倾听，多沟通，尽量满足其合理要求。鼓励患者读书看报接受外界的各种刺激 6. 用药护理所有口服药必须由护理人员按顿送服，以免患者遗忘或错服。 7. 安全护理 （1）防跌倒坠床：指导患者及护理人员注意起居安全，做好防跌倒坠床高危措施。 （2）防自伤：护理人员对患者严密观察，及时排除危险因素，保管好利器，药物等。 （3）防走失：护理人员及家属在患者衣兜内放置患者信息卡，严密看护患者。 【健康指导】 1. 日常生活指导合理安排生活，劳逸结合，戒烟酒。 2. 用药指导规则用药，不可自行减量或停药。 3. 运动指导适当的锻炼如散步、气功、太极等以提高体质，延缓衰老。 . .

阿尔茨海默病治疗药物临床研究技术指导原则

指导原则编号: 治疗阿尔茨海默病药物临床试验 技术指导原则 （第二稿） 二○○七年三月 目录

一、概述 (3) 二、有效性和安全性评价要点 (5) （一）适应症定位 (5) （二）受试人群 (5) （三）有效性评价 (7) （四）安全性评价 (9) （五）临床试验的质量控制 (10) 三、分期试验设计 (10) （一）Ⅰ期临床试验： (10) （二）Ⅱ期临床试验 (12) （三）Ⅲ期临床试验 (13) 四、预防和控制疾病进展药物的临床试验 (14) （一）轻度认知功能损害（MCI）者的临床试验 (14) （二）控制疾病进展药物的临床试验 (15) 五、缩略语 (15) 六、参考文献 (16) 七、著者 (17)

治疗阿尔茨海默病药物临床试验技术指导原则 一、概述 痴呆是一种以认知功能缺损为核心症状的获得性临床综合征，如进行性记忆、思维、语言、行为和人格障碍等，可伴随精神和运动功能障碍，其认知损害的程度足以影响日常生活、社交或职业功能或与个人以前相比有显著下降。痴呆的病因很多，病理生理过程复杂，其中常见的为阿尔茨海默病（AD）、血管性痴呆（VaD）和混合性痴呆。 阿尔茨海默病是一组病因未明的原发性退行性脑变性疾病。多起病于老年期，病程缓慢且不可逆，临床上以智能损害为主，是老年常见病之一。虽然目前尚无“抗痴呆”药物可以治愈此病，但是已有多种对症治疗药物用于临床，一些新的药物也处于研发阶段。 药物临床试验是药物研发中的一个重要环节，是一个目的性和逻辑性极强，并渐次推进的探索循证过程。内容主要包括人体耐受性、药代动力学、药物相互作用、人体药效学、剂量效应探索、疗效确证研究等，按照试验的时间进程又可以分为Ⅰ、Ⅱ、Ⅲ、Ⅳ期等几个阶段。在试验进程中，每项试验均有其特定的目的和研究方法，同时各项试验之间又有着紧密的联系。早期小规模试验的信息用于支持规模更大、目的性更强的后续试验，不同时期或同一时期进行的各项临床试验的信息互为补充，共同构成药物的安全有效性基础。因此，为了高效地开发药物，临床试验的早期就应根据已经掌握的药物特性制定适宜的总体开发计划，在计划中阐明每一项试验的目的、方法、预期结果，计划中应有适当的决策点，阶段性地根据获得的试验结果进行下一步研发决策。

阿尔茨海默症综述

阿尔茨海默病综述 阿尔茨海默病（AD）是一种起病隐匿的进行性发展的神经系统退行性疾病。临床上以记忆障碍、失语、失用、失认、视空间技能损害、执行功能障碍以及人格和行为改变等全面性痴呆表现为特征，病因迄今未明。65岁以前发病者，称早老性痴呆；65岁以后发病者称老年性痴呆。 一．发病机理：该病可能是一组异质性疾病，在多种因素（包括生物和社会心理因素）的作用下才发病。从目前研究来看，该病的可能因素和假说多达30余种，如家族史、女性、头部外伤、低教育水平、甲状腺病、母育龄过高或过低、病毒感染等。下列因素与该病发病有关： 1.家族史 绝大部分的流行病学研究都提示，家族史是该病的危险因素。某些患者的家属成员中患同样疾病者高于一般人群，此外还发现先天愚型患病危险性增加。进一步的遗传学研究证实，该病可能是常染色体显性基因所致。最近通过基因定位研究，发现脑内淀粉样蛋白的病理基因位于第21对染色体。可见痴呆与遗传有关是比较肯定的。 先天愚型（DS）有该病类似病理改变，DS如活到成人发生该病几率约为100%，已知DS致病基因位于21号染色体，乃引起对该病遗传学研究极大兴趣。但该病遗传学研究难度大，多数研究者发现患者家庭成员患该病危险率比一般人群约高3~4倍。 St.George-Hyslop等（1989）复习了该病家系研究资料，发现家庭成员患该病的危险，父母为14.4%；同胞为3.8%～13.9%。用寿命统计分析，FAD一级亲属患该病的危险率高达50%，而对照组仅10%，这些资料支持部分发病早的FAD，是一组与年龄相关的显性常

染色体显性遗传；文献有一篇仅女性患病家系，因甚罕见可排除X-连锁遗传，而多数散发病例可能是遗传易感性和环境因素相互作用的结果。 与AD有关的遗传学位点，目前已知的至少有以下4个：早发型AD基因座分别位于2l、14、1号染色体。相应的可能致病基因为APP、S182和STM-2基因。迟发型AD基因座位于19号染色体，可能致病基因为载脂蛋白E（APOE）基因。 2.一些躯体疾病 如甲状腺疾病、免疫系统疾病、癫痫等，曾被作为该病的危险因素研究。有甲状腺功能减退史者，患该病的相对危险度高。该病发病前有癫痫发作史较多。偏头痛或严重头痛史与该病无关。不少研究发现抑郁症史，特别是老年期抑郁症史是该病的危险因素。最近的一项病例对照研究认为，除抑郁症外，其他功能性精神障碍如精神分裂症和偏执性精神病也有关。曾经作为该病危险因素研究的化学物质有重金属盐、有机溶剂、杀虫剂、药品等。铝的作用一直令人关注，因为动物实验显示铝盐对学习和记忆有影响；流行病学研究提示痴呆的患病率与饮水中铝的含量有关。可能由于铝或硅等神经毒素在体内的蓄积，加速了衰老过程。 3.头部外伤 头部外伤指伴有意识障碍的头部外伤，脑外伤作为该病危险因素已有较多报道。临床和流行病学研究提示严重脑外伤可能是某些该病的病因之一。 4.其他 免疫系统的进行性衰竭、机体解毒功能削弱及慢病毒感染等，以及丧偶、独居、经济困难、生活颠簸等社会心理因素可成为发病诱因。 2该病起病缓慢或隐匿，病人及家人常说不清何时起病。多见于70岁以上（男性平均73岁，女性为75岁）老人，少数病人在躯体疾病、骨折或精神受到刺激后症状迅速明朗化。女性较男性多（女∶男为3∶1）。主要表现为认知功能下降、精神症状和行为障碍、

阿尔兹海默病治疗指南

阿尔茨海默病诊断的新标准和指南 2011-10-27 00:00来源：丁香园 字体大小： 2011年4月19日，以阿尔茨海默病协会和国立卫生院(NIH)的国家老年研究所(NIA)为先锋的三个专家工作组在芝加哥于27年内首次发布了诊断阿尔茨海默病的新标准和指南。 工作组发行了随时可用的4项关于阿尔茨海默病痴呆和由于阿尔茨海默病导致的轻度认知障碍(MCI)的临床诊断标准。提出的一项研究主题是关于临床前的阿尔茨海默病。关于阿尔茨海默病痴呆和由于阿尔茨海默病导致痴呆的生物标记物的使用问题仅作为一项研究议题被提出，此次未意图于其在临床中的使用。 总体而言，阿尔茨海默病诊断指南-扩展阿尔茨海默病定义使其包括此病的两个新的阶段：临床症状前轻度的症状但尚处于痴呆前的阶段；由阿尔茨海默病导致的失智症。这反映了当前的这样的观点：阿尔茨海默病患者在记忆和思维症状出现以前的数十年里脑中可以先产生明显的可测量的变化。 阿尔茨海默病协会首席官员，哲学博士WilliamThies说：“我们希望过去四分之一世纪里科学技术所取得的进步将有助于提高目前的诊断，带动这个领域的更早的检查和治疗，最终导致有效的病性改善疗法”，“这些条目的发展和出版是这个领域的重要的里程碑。也就是说，这些条目的发展和出版不是新的阿尔茨海默病诊断标准发展过程的结束，而是这个过程中重要的一步”。 国家健康协会的阿尔茨海默病中心项目的项目总监，哲学博士CreightonPhelps说“新的指南反映了时下关于脑中导致阿尔茨海默病的关键病理变化和他们与轻度认知障碍及阿尔茨海默病失智症的临床体征之间的关系”，“我们已经可以在临床症状出现前的阶段对这些病理改变进行检测，许多病人在此后很久才出现临床症状。如新指南中所述，随着关于生物标记物的进一步的研究，我们将最终可以预测哪些人具有发展为轻度认知障碍和阿尔茨海默病痴呆的危险，以及哪些人可以从干预措施的发展中获益最多”。 所推荐的新的阿尔茨海默病指南今天由阿尔茨海默病协会主办杂志 Alzheimer’s&Dementia在线出版。纸质版已安排在此杂志的2011年的5月份出版。 阿尔茨海默病的三个分期 目前的阿尔茨海默病的诊断标准通常确定诊断依赖于当个人、家庭或是朋友注意到其在思考、学习和记忆方面的症状。但是研究告诉我们，阿尔茨海默病可能在患者出现症状前数年甚至是数十年已经开始发病。 新的条目涉及阿尔茨海默病随着时间推移发展的三个阶段： ●阿尔茨海默病临床前-可测量的生物标记物（譬如脑部影像学和脑脊液化学检测）的变化在外部的症状可见之前表明疾病最早阶段的征象。目前没有这个阶段的临床诊断标准，但是工作组提供了一个科学的框架帮助研究者更好的定义阿尔茨海默病的这个阶段。 ●由于阿尔茨海默病导致的轻度认知障碍-在记忆和思考能力方面的轻微的变化，足以被注意和评估，但是损害还不至于影响日常活动和功能。 ●由阿尔茨海默病导致的失智症-记忆、思考和行为症状损害到病人的日常生活的躯体功能。为了将来便于对阿尔茨海默病进行症状前治疗，作者认为对疾病最早期的脑的改变进行定义是很重要的，不只是疾病可以看见的、有症状的阶段。作者提出在阿尔茨海默病开始阶段伴随着一个长时期的非症状的阶段，在此阶段脑中有害的变化在进展，具有这些变化的生物标记物证据的个体发展为认知和行为损害的风险及进展为阿尔茨海默病痴呆的风险在增加。

阿尔茨海默症健康管理方案

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阿尔茨海默病 集团企业公司编码：（LL3698-KKI1269-TM2483-LUI12689-ITT289-

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阿尔茨海默病治疗相关靶点研究进展

Pharmacy Information 药物资讯, 2016, 5(1), 1-7 Published Online February 2016 in Hans. https://www.wendangku.net/doc/9a13106531.html,/journal/pi https://www.wendangku.net/doc/9a13106531.html,/10.12677/pi.2016.51001 Research Progress for Relative Treatment Targets in Alzheimer’s Disease Lihua Zhu, Ling He* Department of Pharmacology, College of Pharmacy, China Pharmaceutical University, Nanjing Jiangsu Received: Feb. 10th, 2016; accepted: Feb. 23rd, 2016; published: Feb. 26th, 2016 Copyright ? 2016 by authors and Hans Publishers Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). https://www.wendangku.net/doc/9a13106531.html,/licenses/by/4.0/ Abstract Alzheimer’s disease is neurodegenerative disease mainly characterized by cognitive impairment. Neuron and synapse loss together with neurotransmitter dysfunction have, along with Abdeposi-tion and neurofibrillary tangles, been recognized as hallmarks of AD. However, there is still no a curative treatment for this devastating disease due to complexity of the pathophysiology of the disease. This article reviews relative treatment targets in Alzheimer’s disease from the aspects of main neurotransmitter and receptors in the central nervous system. Keywords Alzheimer’s Disease, Neurotransmitter, G Protein-Coupled Receptors 阿尔茨海默病治疗相关靶点研究进展 诸丽华，何玲* 中国药科大学，药学院，药理系，江苏南京 收稿日期：2016年2月10日；录用日期：2016年2月23日；发布日期：2016年2月26日 *通讯作者。

阿尔茨海默病中医治疗是怎么的

如对您有帮助，可购买打赏，谢谢 阿尔茨海默病中医治疗是怎么的 导语：很多朋友都听说过老年痴呆症，但是对于阿尔茨海默病这种疾病却不了解，甚至没有听说过。其实阿尔茨海默病就是我们常说的老年痴呆症。那么在 很多朋友都听说过老年痴呆症，但是对于阿尔茨海默病这种疾病却不了解，甚至没有听说过。其实阿尔茨海默病就是我们常说的老年痴呆症。那么在西医上，治疗阿尔茨海默这种疾病，一般采取药物治疗，患者长期服用药物控制病情。那么在我国的中医上，治疗这种疾病也有一定的成效，下面我们就来看一下关于阿尔茨海默病中医治疗。 方药：洗心汤加减。方中人参、甘草培补中气；半夏、陈皮健脾化痰；菖蒲、半夏、陈皮以宣窍祛痰；附子协参草以助阳化气，俾正气健旺则痰阻可除；更以茯神、枣仁宁心安神；神曲和胃。本方补正与攻痰并重，补正是益脾胃之气以生心气，攻痰是扫荡干扰心宫之浊邪，再加养心安神之品，以治痴呆。中药针灸治疗原则以补气血，壮心肾，益髓海，开痰窍。 针刺治疗：选穴：第一组：哑门、劳宫、足三里、肾俞。第二组：大椎、鸠尾、三阴交、涌泉。第三组：哑门、十宣、手三里、太冲。三组穴位轮换交替使用，1日1次，细刺治疗。捻转进针法，留针10分钟，运用补的手法，每分钟运针1次，每次运针1分钟。15天为一疗程，每疗程间休息5～7天。 灸法：隔姜灸大椎穴，每次灸3～5壮，隔日1次，10次1疗程，间隔5天继续第2疗程，一般3～4疗程。推拿按摩中西医结合治疗护理康复预防改善劳动环境，预防工业方面的职业病，如重金属铝、一氧化碳。忌酒戒烟。注意饮食、多食维生素C多的食品，坚持学习新知识，保持与社会广泛接触。减轻和推迟记忆力下降的最好办法就是 常识分享，对您有帮助可购买打赏

2013阿尔茨海默症数据及现状

Alzheimer’s Association Report 2013Alzheimer’s disease facts and ?gures Alzheimer’s Association * Abstract This report provides information to increase understanding of the public health impact of Alz-heimer’s disease (AD),including incidence and prevalence,mortality rates,health expenditures and costs of care,and effect on caregivers and society in general.It also explores the roles and unique challenges of long-distance caregivers,as well as interventions that target those challenges.An estimated 5.2million Americans have AD.Approximately 200,000people younger than 65years with AD comprise the younger onset AD population;5million comprise the older onset AD popu-lation.Throughout the coming decades,the baby boom generation is projected to add about 10million to the total number of people in the United States with AD.Today,someone in America develops AD every 68seconds.By 2050,one new case of AD is expected to develop every 33sec-onds,or nearly a million new cases per year,and the total estimated prevalence is expected to be 13.8million.AD is the sixth leading cause of death in the United States and the ?fth leading cause of death in Americans age 65years or older.Between 2000and 2010,the proportion of deaths resulting from heart disease,stroke,and prostate cancer decreased 16%,23%,and 8%,respectively,whereas the pro-portion resulting from AD increased 68%.The number of deaths from AD as determined by of?cial death certi?cates (83,494in 2010)likely underrepresents the number of AD-related deaths in the United States.A projected 450,000older Americans with AD will die in 2013,and a large proportion will die as a result of complications of AD.In 2012,more than 15million family members and other unpaid caregivers provided an estimated 17.5billion hours of care to people with AD and other dementias,a contribution valued at more than $216billion.Medicare payments for services to ben-e?ciaries age 65years and older with AD and other dementias are three times as great as payments for bene?ciaries without these conditions,and Medicaid payments are 19times as great.Total payments in 2013for health care,long-term care,and hospice services for people age 65years and older with dementia are expected to be $203billion (not including the contributions of unpaid caregivers).An estimated 2.3million caregivers of people with AD and other dementias live at least 1hour away from the care recipient.These “long-distance caregivers”face unique challenges,including dif?culty in assessing the care recipient’s true health condition and needs,high rates of family disagreement regarding caregiving decisions,and high out-of-pocket expenses for costs related to caregiving.Out-of-pocket costs for long-distance caregivers are almost twice as high as for local caregivers.ó2013The Alzheimer’s Association.All rights reserved. Keywords: Alzheimer’s disease;Dementia;Diagnostic criteria;Prevalence;Incidence;Mortality;Caregivers;Family care-giver;Spouse caregiver;Health care costs;Health care expenditures;Long-term care costs;Medicare spending;Medicaid spending;Long-distance caregiver;Activities of daily living;Instrumental activities of daily living 1.About this report 2013Alzheimer’s Disease Facts and Figures is a statisti-cal resource for US data related to Alzheimer’s disease (AD),the most common type of dementia,as well as other dementias.Background and context for interpretation of the data are contained in the Overview.This information includes de?nitions of the various types of dementia and a summary of current knowledge about AD.Additional sections address prevalence,mortality,caregiving,and use and costs of care and services.This special report fo-cuses on long-distance caregivers of people with AD and other dementias. Speci?c information in this year’s Alzheimer’s Disease Facts and Figures includes the following: *Corresponding authors:William Thies,Ph.D.,and Laura Bleiler.Tel.:312-335-5893;Fax:866-521-8007.E-mail address:lbleiler@https://www.wendangku.net/doc/9a13106531.html, 1552-5260/$-see front matter ó2013The Alzheimer’s Association.All rights reserved. https://www.wendangku.net/doc/9a13106531.html,/10.1016/j.jalz.2013.02.003 Alzheimer’s &Dementia 9(2013)208–245