阿尔茨海默症调研

蔚落 2022-09-10 10:18 163阅读 0赞

### 老年痴呆类型 ###

一、阿尔茨海默症(Alzheimer)的痴呆，是最常见的痴呆，目前病因还不是非常清楚，患者痴呆的程度是逐渐进展，额颞叶的慢性过程。  
二、精神内分泌疾病引发的脑痴呆，例如甲亢、焦虑、抑郁、精神刺激或者药物中毒等引起的老年痴呆病症。  
三、血管性痴呆，因为脑血管病反复出现的脑出血、脑梗塞以及脑梗死等，都可以导致脑血管病的后遗症，出现认知功能下降等老年痴呆的症状。  
四、单纯性痴呆，随着患者的年龄的增长，机体各方面器官功能逐渐减退，从而出现痴呆的症状。

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**阿尔茨海默症(Alzheimer's disease)**

①β蛋白

②τ蛋白

根据国外的发展：*Current treatment approaches focus on maintaining the mental function, managing behavioral symptoms, and slow or delay the disease progression.（也就是说只能控制和延缓）*

阿尔茨海默症被认为是由β-amyloid淀粉样蛋白的累积引起的，这种蛋白累积诱导神经元蛋白τ聚集，继而发生神经退行性病变。

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### 预防 ###

The recommendation is 30 minutes of moderately vigorous aerobic exercise, three to four days per week.(每周保持有氧运动)\[5\]

A combination of 15 μM trans-chalcone and 8 μM baicalein was found to be the most synergistic combination\[7\](反式查尔酮+黄岑可以减少阿尔茨海默症中Aβ42导致的氧化损伤)

By using a specific inhibitor of the 1,25 D3-vitamin D( 维生素D3) receptor, the researchers2 were able to show that phagocytosis of amyloid beta in patients with type I and type II macrophages was dependent on 1,25 D3\[8\]

Curcuminoids(姜黄素) have been reported to have neuroprotective effects in other papers.\[8\]

In that recent paper, curcuminoids (curcumin, demethoxycurcumin, and bisdemethoxycurcumin) promoted neurite outgrowth from PC12 cells (a rat pheochromocytoma cell line) via complex signaling involving MAPK/ERKand PKC-dependent pathways.\[8\](在最近的论文中，姜黄素类物质（姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素）通过涉及MAPK/ERK和PKC依赖途径的复杂信号传导促进PC12细胞（大鼠嗜铬细胞瘤细胞系）的神经轴突生长。)

For example, a recent papera reported on an FDA approved drug (Bexarotene†) that was able to reduce Abeta plaque area in a mouse model of AD by more than 50% within just 72 hours\[8\](Bexarotene†在72小时内能减少50%以上的Aβ蛋白)

Scientists found that when they added the compounds -- called advanced glycation end products (AGEs) -- to the lifelong diets of laboratory mice, the animals developed greater amounts of beta-amyloid in the brain.\[9\](AGES产物有利于粥样蛋白的产生)

Sleep deprivation increases Alzheimer’s protein\[11\]（睡眠不足会导致粥样蛋白加速生成）

In other research, scientists have identified ways that essential omega-3 fatty acid -- docosahexaenoic acid (DHA) or fish oil -- can help prevent Alzheimer's.

"Not only does caffeine appear to offer promise as an effective treatment against Alzheimer's, but our prior work has determined that the same daily amount of caffeine protects Alzheimer's mice from even getting memory impairment to begin with, when caffeine treatment is started in young adulthood(咖啡有助于逆转阿尔茨海默症)\[12\]

Copper adheres strongly to amyloid and may promote its accumulation and toxicity. The accumulation of copper in brain blood vessels over a long period may reduce carrier protein levels and contribute to toxic amyloid accumulation in the brain, which consequently kills brain cells, as seen in Alzheimer's.（铜有助于加重阿尔茨海默症）\[12\]

No one diet is best. Two diets that have been studied and may be beneficial to lowering the risk of Alzheimer's are the DASH (Dietary Approaches to Stop Hypertension) diet and the Mediterranean diet.(没有最佳饮食，目前研究过有助于阿尔茨海默症的是DASH饮食和地中海饮食)\[17\]

In other research, scientists have identified ways that essential omega-3 fatty acid -- docosahexaenoic acid (DHA) or fish oil -- can help prevent Alzheimer's. This substance is found in fatty fish like salmon.  
"Our study shows that the memory impairment of aged Alzheimer's mice was completely reversed by giving them caffeine, the human equivalent of five daily cups of coffee, in their drinking water," Arendash says. In addition, evidence of Alzheimer's in the brains of mice given caffeine was found to be substantially decreased, indicating that caffeine has a direct effect on the Alzheimer's disease process and is not simply masking symptoms. On the basis of these studies in Alzheimer's mice, the Byrd Alzheimer's Institute has begun Phase II clinical trials with caffeine in aged humans.(咖啡因对大脑有直接影响)

1. Get More Sleep to Reduce Beta Amyloid Protein in the Brain
    
    
    A good night’s sleep is important not just for clearer thinking the next day but clearer thinking and better memory as you age.
    
    A 2014 study from the University of Wisconsin shows poor nights’ sleep can reduce the body’s efficiency in removing beta amyloid proteins. In the study those who reported problems with sleep had more amyloid deposits in their brain, particularly in the area of the brain responsible for memory, thought and awareness.
    
    
    A 2012 study by Washington University School of Medicine in St. Louis also found that people who had trouble sleeping in middle age were more likely to suffer from a buildup of amyloid proteins that leads to Alzheimer’s.
    
    People who woke up more than five times an hour and spent less than 85 percent of their time in bed actually sleeping were more likely to have abnormal levels of beta amyloid protein plaques.
    
    
    2. Is Sleeping on Your Side Best for Removing Beta Amyloid Proteins?
    
    
    Sleeping on your side helps clear out destructive beta amyloid proteins from the brain more efficiently than sleeping on your back or stomach, says a 2015 study from Stony Brook University.
    
    The systems for clearing proteins are more efficient when you are asleep, as shown by the studies above, but it seems that side-sleeping is the best position to take, although the results of this animal study have yet to be replicated in human research. (Read more about the brain lymph system that cleans your brain each night.)
    
    
    3. Cut Your Copper Intake to Reduce Beta Amyloid Proteins
    
    
    Copper in the diet can reduce the body’s ability to clear away beta amyloid proteins, according to a 2013 study from the University of Rochester Medical Center – and even the small amounts of copper that are found in the average diet can make a difference.
    
    Copper is an essential trace element and it helps to form red blood cells as well as protect the immune system. But it can also build up in the brain and prevent the easy clearance of beta amyloid proteins, according to researchers.
    
    4. Bursts of Brain Activity Help Reduce Beta Amyloid Formation
    
    
    Spikes and bursts of activity in the brain help to regulate the formation of beta amyloid proteins in the brain, according to a 2013 study from Tel Aviv University's Sackler Faculty of Medicine – experiencing different environments and different activities can cause spiking patterns in the brain.
    
    Researchers suggest that a stimulating environment and changes in sensory experiences can help to reduce the levels of harmful beta amyloid protein in the brain.
    
    5. Take Vitamin D to Reduce Beta Amyloid in the Brain?
    
    
    Certain mechanisms between brain cells can be better regulated with the help of vitamin D3, which will help the body get rid of beta amyloid protein according to a 2012 study by the David Geffen School of Medicine at UCLA.
    
    Vitamin D3 may help activate signaling networks between cells to stimulate the immune system to clear beta amyloid proteins.
    
    
    6. Eat Curcumin to Reduce Beta Amyloid Build-Up
    
    7. Increase Your Intake of Omega 3 Fatty Acids to Remove Amyloid Proteins
    
    
    Another study from the David Geffen School of Medicine at UCLA in 2013 reveals how omega 3 fatty acids help boost the immune system to clear the brain of beta amyloid protein.
    
    Omega 3 fatty acids are found in fish and plant oils and a particular fatty acid called omega-3 DHA (docosahexaenoic acid) helps regulate inflammation and get rid of the troubling proteins, according to scientists.

①充足的睡眠

②侧卧

③减少铜摄入量

④头脑风暴（多思考）

⑤维生素D3

⑥姜黄素

⑦OMEGA-3摄入

上述内容来自\[19\]

Research in 2015 from Washington University in St. Louis shows that older people take longer to get rid of beta amyloid proteins from their brains, with people aged in the 30s taking around four hours to clear half the beta amyloid protein while those aged over 80 take more than 10 hours. When beta amyloid is not shifted from the brain it clumps and disrupts brain function.\[19\](30岁的人需要4个小时来清理一半数量的β蛋白)

Curcumin is a component in turmeric, the spice that is used to flavor and color curry, and scientists have shown that it can help your immune system clear beta amyloid protein from the brain. Curcumin is known for its antioxidant and anti-inflammatory properties, according to a 2006 study from the David Geffen School of Medicine at UCLA, and in the test tube curcumin improved the removal of amyloid protein by immune cells in 50 percent of patients suffering from Alzheimer’s disease.

Another study from the David Geffen School of Medicine at UCLA in 2013 reveals how omega 3 fatty acids help boost the immune system to clear the brain of beta amyloid protein.\[19\](姜黄素和omega3DHA（二十二碳六烯酸）有助于大脑去除β蛋白)

In addition to preventing the toxicity of beta-amyloid to brain cells, rosmarinic acid(迷迭香酸) has also been found to both inhibit the formation of beta-amyloid AND destabilize and dissolve beta-amyloid fibrils that have already formed. These results were so impressive that the researchers concluded that rosmarinic acid “could be a key molecule for the development of therapeutics for Alzheimer’s disease.”15  
Another recent study also showed that rosmarinic acid exerts a calming effect on the mind while supporting short and long term memory.16

This is an added bonus for anybody.\[20\]

A study published in the May 2004 issue of the Journal of Neuroinflammation reported that brain cells pre-treated with ginkgo extract and then exposed to beta-amyloid protein were resistant to the toxic effects of beta-amyloid and survived without damage.

A study at Georgetown University Medical Center, Washington, D.C., found that nerve cells exposed to beta-amyloid displayed free radical production, and cellular death. On the other hand, after they had been pre-treated with ginkgo biloba extract, free radical production, and cellular damage and death were all inhibited.

Likewise, a study at the University of Southern Mississippi found that brain cells treated with ginkgo biloba extract were resistant to the damaging effects of beta-amyloid.(银杏提取物能让脑细胞对β蛋白的毒性具备抵抗力)

What happens to the brain of a person with Alzheimer’s?  
The brain is made up of 100 billion neurons. In the Alzheimer’s brain, neurofibrillary tangles and amyloid plaques disable the cell’s ability to communicate. These plaques contain beta-amyloid, a protein that releases free radicals, or highly reactive molecules that can cause damage to cells through a process called oxidation. These free radicals are believed to lower levels of acetylcholine (a brain chemical that helps transmit impulses in the nervous system) and damage brain tissue, bringing on the symptoms of Alzheimer’s disease.（自由基会降低乙酰胆碱的水平，从而影响大脑）

Since numerous studies have shown that ginkgo biloba extract has a beneficial effect on Alzheimer’s disease, its effect on the exposure of brain cells to beta-amyloid protein has also been investigated, and the results are very promising. A study published in the May 2004 issue of the Journal of Neuroinflammation reported that brain cells pre-treated with ginkgo extract and then exposed to beta-amyloid protein were resistant to the toxic effects of beta-amyloid and survived without damage.

RED GINSENG EXTRACT  
Also called panax ginseng, red ginseng is an adaptogen—an herb used to help individuals cope with physical and emotional stress—and is the most commonly used Asian ginseng. Thousands of studies have demonstrated that ginseng supports a myriad of health concerns ranging from maintaining normal glucose levels to stimulating immune function. Red ginseng extract has also been found to benefit cognitive function. Two ginseng phytochemicals in particular—ginsenosides Rb1 and Rg1—have demonstrated the ability to improve memory in Alzheimer’s disease-model mice, both in vivo and in vitro.20

A study at the China Academy of Traditional Chinese Medicine, Beijing, focused on the effects of a combination of ginseng and ginkgo extracts on the brain neurotransmitter acetylcholine in laboratory animals, whose brains had been injected with beta-amyloid. Therapeutic strategies in Alzheimer’s disease are largely aimed at increasing available acetylcholine.（银杏提取物和红参提取物能提高乙酰胆碱的水平）

Recent Japanese studies even showed that in addition to improving memory, the ginseng extracts were able to regenerate brain axons and synapses in laboratory animals. This is highly significant because these brain cells are typically destroyed by Alzheimer’(日本最近的研究甚至表明，人参提取物除了能改善记忆外，还能在实验动物体内再生脑轴突和突触。这一点非常重要，因为这些脑细胞通常会被阿尔茨海默氏症破坏)

This may help to explain why the incidence of Alzheimer’s disease is much lower in India than in the West.

In fact, according to an on-line BBC article called “Curry May Slow Alzheimer’s” (Nov. 21, 2001),32 previous studies have found that Alzheimer’s affects just 1% of people over the age of 65 living in some Indian villages.

Curcumin got a lot of press coverage a couple of years ago when researchers at the University of California at Los Angeles announced that it reduced Alzheimer’s-like brain changes in mice that were injected with beta-amyloid to create conditions like those that exist in patients with the disease. They found that curcumin helped to clear amyloid from the brain and that its relative lack of side effects and combined anti-inflammatory and antioxidant properties could be beneficial to Alzheimer’s patients.(印度阿尔茨海默症的得病率很低，可能取决于姜黄素和咖喱的摄入)

In two very recent studies at the Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Japan, the same Japanese researchers found an improvement in the memory of laboratory animals that had been injected with beta-amyloid. The ashwagandha also prevented a loss of axons, dendrites and synapses—all vital to normal brain function.45

Even more remarkable, in another study, animals whose brains had been severely damaged by beta-amyloid injections, the oral administration of withanolide-A derived from ashwagandha regenerated almost completely the damaged brain connections. In fact, the author’s concluded that, “Withanolide-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.”  
Thus, the active components of ashwagandha may actually be able to reverse damage caused beta-amyloid and regenerate vital neural connections.(ashwagandha 阿育吠陀药物)

翻译如下:

**大脑因注射β-淀粉样蛋白而严重受损的动物，口服从ashwagandha中提取的withanolide-A几乎完全再生了受损的大脑连接。事实上，作者的结论是，“Withanolide-A因此是神经退行性疾病治疗的重要候选药物，因为它能够重建神经网络。”**

因此，ashwagandha的活性成分实际上可能能够逆转β淀粉样蛋白引起的损伤，并再生重要的神经连接

HUPERZINE(石杉碱)  
Huperzine, an alkaloid extracted from a Chinese moss, Huperzia serrata, has a long history of use in traditional chinese medicine. It is showing great promise as a therapeutic treatment for Alzheimer’s disease and other memory loss disorders, and has been approved as a drug in China to treat Alzheimer’s disease and other age-associated memory impairments. In fact, clinical trials in China have demonstrated that huperzine significantly relieves memory deficits in the elderly due to Alzheimer’s disease and vascular dementia, without the side effects that usually accompany pharmaceutical acetylcholinesterase inhibitors.

FERULIC ACID(阿魏酸)  
Ferulic acid is a phytochemical with anti-inflammatory and antioxidant properties that is found in foods such as brown rice, wheat, oats, coffee, apples, artichokes, peanuts, oranges, and pineapple. Ferulic acid has a chemical structure that is very similar to that of curcumin.

A number of in vitro studies done in the past few years in Japan,37 Korea,41 and the United States,40 all found that it protects neuronal cells from the damaging effects of beta-amyloid.

Two other studies also showed that pre-treatment with ferulic acid protected laboratory animals that had been injected with beta-amyloid from learning and memory deficits. In a study at the Institute of Natural Medicine, Hallym University, Chunchon, South Korea, mice were allowed free access to drinking water containing ferulic acid for four weeks, before being injected with beta-amyloid. The control mice, which were injected with the beta-amyloid but did not have access to ferulic acid, exhibited impaired performance on memory and behavior tests, whereas, the mice treated with ferulic acid were protected from the decrease in performance skills.

The scientists concluded that these results demonstrate that long-term administration of ferulic acid induces resistance to beta-amyloid toxicity in the brain, and suggest that it may be a useful preventive against Alzheimer’s disease.

（阿魏酸的化学结构与姜黄素非常相似。科学家得出结论，这些结果表明，长期服用阿魏酸可诱导大脑对β-淀粉样蛋白毒性产生抵抗，并表明阿魏酸可能是预防阿尔茨海默病的有效药物）

MYRICETIN(杨梅素)  
Myricetin is a flavonoid that is commonly found in foods such as berries, vegetables, teas, wine, and herbs. Research has shown that myricetin has antioxidant and anti-inflammatory properties, and now, although the exact mechanism is unclear, scientists at the Kanazawa University School of Medical Science in Japan have found that myricetin also has the ability to inhibit the accumulation of beta-amyloid protein.37

Additionally, these researchers also found that like rosmarinic acid and curcumin, myricetin was extremely effective in not only preventing the build up of beta-amyloid deposits in the brain, but that it could also dissolve beta-amyloid deposits that had previously formed.

This type of therapeutic strategy is of great interest to researchers trying to develop a means of not only preventing the formation of amyloid plaques, but also removing preformed amyloid deposits.

VINPOCETINE(长春西汀)  
Vinpocetine, derived from the periwinkle plant Vinca minor, is also showing a number of neuroprotective properties that may help in the treatment of Alzheimer’s and other neurodegenerative disorders in which oxidative stress is involved. It is an antioxidant and vasodilator, increasing blood flow to the brain,28 and researchers from the University of Coimbra in Portugal found that it helps prevent oxidative stress in cells treated with beta-amyloid.29

上述内容都来自于\[20\]

Benfotiamine([苯磷硫胺][Link 1]) has been beneficial in a rodent study.  
   Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice.  
   Brain. 2010; Department of Neurology, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.  
   Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, **benfotiamine** dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, it effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. In the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities.（在这里，我们在阿尔茨海默病小鼠模型（淀粉样前体蛋白/早老素-1转基因小鼠）中测试了生物利用度优于硫胺素的硫胺素衍生物苯氟硫胺对认知障碍和病理改变的影响。我们在Morris水迷宫实验中发现，经过8周的慢性治疗后，[苯磷硫胺][Link 1]剂量依赖性地增强了淀粉样前体蛋白/早老素-1小鼠的空间记忆。此外，它有效地减少了转基因小鼠大脑皮质区域的淀粉样斑块数量和磷酸化tau水平）

Carnosine(肌肽) is a potent antixodiant and could be of benefit in reducing amyloid formation.\[21\]

CoQ10, or coenzyme Q10, may be of benefit.(Q10)

Curcumin, an extract from turmeric, may be helpful.(姜黄素也许会有帮助)

Fish oils, including EPA and DHA omega-3 fatty acids should be considered.（鱼油和omega-3）

Hypericum perforatum, known as St. John's wort(圣约翰草). In a microglial cell line pretreated with St. John's wort extract, the cell death evoked by treatment with amyloid-beta was attenuated significantly in a dose-dependent manner.

Myricetin（杨梅素）inhibits beta-amyloid fibril formation, a key problem with Alzheimer's disease.

Uncaria(钩藤) rhynchophylla could be of benefit.

Benefit of deep sleep  
People who miss a night of sleep have a buildup in their brain of beta-amyloid. This substance is linked to Alzheimer’s disease.（深度睡眠）

Neurosci Lett. 2009; **[Hibifolin][], a flavonol glycoside(一种黄酮醇苷)**, prevents beta-amyloid-induced neurotoxicity in cultured cortical neurons.\[21\]（该物品目前国内禁止医用）

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### 治疗 ###

patients who undergo hemodialysis maintain or show improved cognitive functions, and longer periods of hemodialysis are correlated with reduced dementia risk(血液透析对β蛋白进行过滤，来有利于大脑清除β蛋白)\[6\]

Bexarotene†\[8\]

THC(四氢大麻酚) reduces beta amyloid proteins in human neurons \[10\]

Previous pre-clinical studies have shown that administration of THC at 3mg/kg per day for four weeks lead to a reduction in Aß plaques and preservation of neurons. Additionally, according to research in human dementia patients, administration of synthetic THC analog, dronabinol (2.5mg) daily for two weeks improved neuropsychiatric profiles for agitation and aberrant motor and night time behaviours.(服用THC治疗有明显改善)\[13\]

Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice\[14\]（咖啡因和adenosine A(2a) receptor腺苷A（2a）受体预防β蛋白）

Prolonged treatment with caffeine (1 mg/ml) had no effect alone but prevented the Abeta-induced cognitive impairment in both tasks when associated with acute caffeine (30 mg/kg) 30 min treatment before Abeta administration. \[14\]（只服用咖啡因无效）

in June 2021, the FDA approved a pharmaceutical called Aducanumab\[15\]（一种叫做Aducanumab的药物）

There are a number of strategies being developed by those on the front line of research. The first: Decrease beta-amyloid production. Researchers at Elan Pharmaceuticals in South San Francisco and Eli Lilly and Co. in Indianapolis have found a new class of drugs that decrease beta-amyloid production by blocking gamma-secretase, an enzyme that separates beta-amyloid from a larger protein and releases it into the brain.(一类新的药物，通过阻断γ-分泌酶来减少β淀粉样蛋白的产生，γ-分泌酶是一种将β淀粉样蛋白从较大的蛋白质中分离出来并释放到大脑中的酶)

"Gamma-secretase is a critical target for treatment of Alzheimer's disease, as beta-amyloid is the core building block of the plaque," Dale B. Schenk, PhD, vice president of discovery research at Elan, tells WebMD. "This work is a stepping stone toward treatments that will eventually enter the clinic."

Another strategy is to prevent beta-amyloid buildup and the toxic damage it causes. Metals in the brain, such as copper and zinc, bind to beta-amyloid, causing it to accumulate in Alzheimer's and trigger reactions that release toxic byproducts, which can create more damage. Researchers at Harvard University in Boston used drugs called chelators to trap copper and zinc, and tested them in an animal model.

When mice were given copper and zinc chelators by mouth for 12 weeks, beta-amyloid accumulation decreased so dramatically that some treated animals had none left.(铜和锌螯合剂)\[16\]

**In late stages of Alzheimer's disease, there is so much damage to both nerve cells and their connections that removing beta-amyloid would be futile, explains the Hopkins' researcher. "There's no sense in trying the vaccine in someone who's been in a nursing home for 10 years."\[16\]（晚期阿尔茨海默症治疗无效，因为神经已经收到损害）**

Eprodisate(埃普罗地酸) belongs to a new class of drugs that blocks amyloid build-up in various tissues by inhibiting the interactions of amyloidogenic proteins and glycosaminoglycans. \[21\]

Aducanumab, an antibody that binds to both insoluble forms of beta amyloid   
(amyloid plaques) and soluble forms, reduced levels of beta-amyloid in the brain and   
slowed the rate of cognitive decline in a group of people who had mild or preclinical \[3\](Aducanumab降低阿尔茨海默症的进程)

鼠尾草、姜黄、银杏叶、南非醉茄、人参、积雪草、柠檬香膏\[22\]

研究人员发现以中药**黄连、黄芩、黄柏和栀子**所组成、可治疗脑缺血的传统中药名方“黄连解毒汤”，在剔除黄芩后，明显降低了“β-淀粉样蛋白”的水平。他们也发现治疗疼痛和神经痛的中药复方“元胡止痛散”中的主要中药**延胡索**，能降低“过度磷酸化Tau蛋白”的水平。研究团队通过数据分析和建模技术，将6种中药以不同比例组合成24款中药复方，并将效果最佳的复方命名为“神经防御方”。

研究团队其后完成了阿尔茨海默症小鼠模型临床前实验。结果显示，小鼠服用“神经防御方”后，其“β-淀粉样蛋白”聚集和异常“过度磷酸化Tau蛋白”的沉积水平，均明显地下降三至四成。“神经防御方”也有效地改善了患病小鼠的记忆力和学习能力，以及记忆衰退症状。\[27\]

姜黄素提高巨噬细胞对Aβ的吞噬能力\[28\]

Curcuminoids, polyphenol compounds from turmeric (Curcuma longa), possess diverse biological properties that modulate debilitating biochemical processes involved in AD that include attenuation of mitochondrial dysfunction-induced oxidative stress and inflammatory responses to inflammatory cytokines, COX-2, and iNOS. Curcuminoids also bind to β-amyloid (Aβ) plaques to inhibit amyloid accumulation and aggregation in the brain, in addition to inhibiting the toxic Aβ oligomer formation and oligomer-dependent Aβ toxicity. These properties can be further elaborated to DS, glaucoma and AMD\[29\](姜黄素是姜黄（姜黄）中的多酚化合物，具有多种生物学特性，可调节AD中的衰弱生化过程，包括减轻线粒体功能障碍诱导的氧化应激和炎症细胞因子、COX-2和iNOS的炎症反应。姜黄素还与β-淀粉样蛋白（Aβ）斑块结合，以抑制大脑中淀粉样蛋白的积累和聚集，此外还抑制毒性Aβ低聚物的形成和低聚物依赖性Aβ毒性。）

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总结：

相关食物是

尽量减少食物中AGES的摄入  
姜黄素(姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素,类似化学结构起作用的还有阿魏酸)  
反式查尔酮+黄岑  
维生素D3  
omega-3（DHA-二十二碳六烯酸）  
充足的睡眠(侧卧)  
少铜  
勤于思考  
迷迭香  
银杏叶提取物  
印度红参（ashwagandha）  
石杉碱(记忆力)  
杨梅素  
长春西汀  
鼠尾草、南非醉茄、人参、积雪草、柠檬香膏

\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#

阿尔茨海默症分为两部分

①毒蛋白的处理问题

<table style="width:500px;"> 
 <tbody> 
  <tr> 
   <td><strong>亚型</strong></td> 
   <td><strong>生成顺序</strong></td> 
   <td><strong>位置</strong></td> 
   <td><strong>毒性</strong></td> 
   <td><strong>疾病名称</strong></td> 
  </tr> 
  <tr> 
   <td>Aβ40</td> 
   <td>Aβ40含量是Aβ42的10-20倍</td> 
   <td>脑血管斑块</td> 
   <td>相对小</td> 
   <td>大脑淀粉样血管病变</td> 
  </tr> 
  <tr> 
   <td>Aβ42</td> 
   <td></td> 
   <td> <p>更容易聚集</p> <p>实质斑块</p> </td> 
   <td>更毒</td> 
   <td></td> 
  </tr> 
 </tbody> 
</table>

Aβ40量大为主，也是先产生

Aβ42量小，后产生\[24\]

②神经被毒蛋白攻击+自身的衰老问题

人体内的ApoE主要有三个亚型：E2，E3和E4

一些研究提出，Aβ蛋白与神经元膜的相互作用是AD中观察到的神经元死亡的原因。\[26\]

\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#后续补充\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#\#

\[30\]怀疑姜黄素基本无效（因为提取物中有十几种分子）

\[31\]认为不要质疑所有的姜黄素临床数据

\[32\]中认为银杏叶无效

***Reference:***

*\[1\]*[发现阿尔茨海默症相关新蛋白 - 生物通 (ebiotrade.com)][- _ _ebiotrade.com]

\[2\][Mitochondrial Repair Diet (healthfully.com)][Mitochondrial Repair Diet _healthfully.com]

\[3\][Beta-amyloid and the Amyloid Hypothesis (alz.org)][Beta-amyloid and the Amyloid Hypothesis _alz.org]

\[4\][Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer’s disease mouse model with suppression of glymphatic clearance | Alzheimer's Research & Therapy | Full Text (biomedcentral.com)][Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer_s disease mouse model with suppression of glymphatic clearance _ Alzheimer_s Research _ Therapy _ Full Text _biomedcentral.com]

\[5\][What can you do to avoid Alzheimer’s disease? - Harvard Health][What can you do to avoid Alzheimer_s disease_ - Harvard Health]

\[6\][Beta Amyloid - an overview | ScienceDirect Topics][Beta Amyloid - an overview _ ScienceDirect Topics]

\[7\][(PDF) Trans-Chalcone Plus Baicalein Synergistically Reduce Intracellular Amyloid Beta (Aβ42) and Protect from Aβ42 Induced Oxidative Damage in Yeast Models of Alzheimer’s Disease (researchgate.net)][PDF_ Trans-Chalcone Plus Baicalein Synergistically Reduce Intracellular Amyloid Beta _A_42_ and Protect from A_42 Induced Oxidative Damage in Yeast Models of Alzheimer_s Disease _researchgate.net]

\[8\][Natural Products to Clear Amyloid Beta From the Brain | Life Enhancement Products (life-enhancement.com)][Natural Products to Clear Amyloid Beta From the Brain _ Life Enhancement Products _life-enhancement.com]

\[9\][Amyloid disease natural alternatives, herbs to stop plaque (raysahelian.com)][Amyloid disease natural alternatives_ herbs to stop plaque _raysahelian.com]

\[10\][Cannabinoids remove plaque-forming Alzheimer’s proteins from brain cells - Salk Institute for Biological Studies][Cannabinoids remove plaque-forming Alzheimer_s proteins from brain cells - Salk Institute for Biological Studies]

\[11\][Sleep deprivation increases Alzheimer’s protein | National Institutes of Health (NIH)][Sleep deprivation increases Alzheimer_s protein _ National Institutes of Health _NIH]

\[12\][Staving Off Alzheimer's Disease With The Right Diet, Prescriptions -- ScienceDaily][Staving Off Alzheimer_s Disease With The Right Diet_ Prescriptions -- ScienceDaily]

\[13\][How to Prevent Dementia: The Role of Cannabinoid Therapy (rxleaf.com)][How to Prevent Dementia_ The Role of Cannabinoid Therapy _rxleaf.com]

\[14\][Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cognitive deficits in mice - PubMed (nih.gov)][Caffeine and adenosine A_2a_ receptor antagonists prevent beta-amyloid _25-35_-induced cognitive deficits in mice - PubMed _nih.gov]

\[15\][How to Prevent Dementia: The Role of Cannabinoid Therapy (rxleaf.com)][How to Prevent Dementia_ The Role of Cannabinoid Therapy _rxleaf.com]

\[16\][Fighting Alzheimer's Disease: Go for the Beta-Amyloid! (webmd.com)][Fighting Alzheimer_s Disease_ Go for the Beta-Amyloid_ _webmd.com]

\[17\][Can Alzheimer's be Prevented? | Alzheimer's Association][Can Alzheimer_s be Prevented_ _ Alzheimer_s Association]

\[18\][Staving Off Alzheimer's Disease With The Right Diet, Prescriptions -- ScienceDaily][Staving Off Alzheimer_s Disease With The Right Diet_ Prescriptions -- ScienceDaily]

\[19\][7 Tips to Reduce Amyloid Proteins in Your Brain (zoomhealth.net)][7 Tips to Reduce Amyloid Proteins in Your Brain _zoomhealth.net]

\[20\][Clear Your Brain of the Toxic Gunk that Causes Alzheimer’s Disease! – Us Smart Publications (smart-publications.com)][Clear Your Brain of the Toxic Gunk that Causes Alzheimer_s Disease_ _ Us Smart Publications _smart-publications.com]

\[21\][Amyloid disease natural alternatives, herbs to stop plaque (raysahelian.com)][Amyloid disease natural alternatives_ herbs to stop plaque _raysahelian.com]

\[22\][7 Best Herbs and Spices for Brain Health (verywellmind.com)][7 Best Herbs and Spices for Brain Health _verywellmind.com]

\[23\][Nat Commun：Aβ42/40比例的调控或成阿尔茨海默病治疗关键|阿尔茨海默病|aβ|细胞 (qq.com)][Nat Commun_A_42_40_a_ _qq.com]

\[24\][(19 条消息) 关于用大鼠进行阿尔兹海默症相关实验中为什么采用Aβ40而不是Aβ42？ - 知乎 (zhihu.com)][19 _ _A_40_A_42_ - _ _zhihu.com]

\[25\][解读Acta Neuropathologica︱早发性AD中的一种特殊斑块: 粗糙-颗粒状斑块 - 知乎 (zhihu.com)][Acta Neuropathologica_AD_ _-_ - _ _zhihu.com]

\[26\][Nat Commun:  Aβ蛋白结构揭示其毒性 - 生物研究专区 - 生物谷 (bioon.com)][Nat_Commun_A_ - _ - _ _bioon.com]

\[27\][香港浸大研发中药新复方有助治疗阿尔茨海默症-新华网 (xinhuanet.com)][-_ _xinhuanet.com]

\[28\][Curcuminoids enhance amyloid-β uptake by macrophages of Alzheimer's disease patients - IOS Press][Curcuminoids enhance amyloid-_ uptake by macrophages of Alzheimer_s disease patients - IOS Press]

\[29\][Curcuminoids in neurodegenerative diseases - PubMed (nih.gov)][Curcuminoids in neurodegenerative diseases - PubMed _nih.gov]

\[30\][Deceptive curcumin offers cautionary tale for chemists | Nature][Deceptive curcumin offers cautionary tale for chemists _ Nature]

\[31\][Don't discount all curcumin trial data | Nature][Don_t discount all curcumin trial data _ Nature]

\[32\][银杏叶不能预防阿尔茨海默病\_阿尔茨海默病\_银杏叶\_医脉通 (medlive.cn)][_medlive.cn]

[Link 1]: http://www.baidu.com/link?url=V3f6dD1l021IzrkTM7jzTnZhJAJuyBSEFukAwjMX2bxT8-tYIrfCYRQ4OQDtsKackPBCLDP9qk1vEd0rjlcITbNTQ0UKeko9fjqPLKCDrUrIwYlUuKRx3AawNa8omdfG
[Hibifolin]: https://www.raysahelian.com/hibifolin.html
[- _ _ebiotrade.com]: http://www.ebiotrade.com/newsf/2012-6/2012615105400331.htm
[Mitochondrial Repair Diet _healthfully.com]: https://healthfully.com/mitochondrial-repair-diet-5694238.html
[Beta-amyloid and the Amyloid Hypothesis _alz.org]: https://www.alz.org/national/documents/topicsheet_betaamyloid.pdf
[Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer_s disease mouse model with suppression of glymphatic clearance _ Alzheimer_s Research _ Therapy _ Full Text _biomedcentral.com]: https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00688-1
[What can you do to avoid Alzheimer_s disease_ - Harvard Health]: https://www.health.harvard.edu/alzheimers-and-dementia/what-can-you-do-to-avoid-alzheimers-disease
[Beta Amyloid - an overview _ ScienceDirect Topics]: https://www.sciencedirect.com/topics/neuroscience/beta-amyloid
[PDF_ Trans-Chalcone Plus Baicalein Synergistically Reduce Intracellular Amyloid Beta _A_42_ and Protect from A_42 Induced Oxidative Damage in Yeast Models of Alzheimer_s Disease _researchgate.net]: https://www.researchgate.net/publication/354267256_Trans-Chalcone_Plus_Baicalein_Synergistically_Reduce_Intracellular_Amyloid_Beta_Ab42_and_Protect_from_Ab42_Induced_Oxidative_Damage_in_Yeast_Models_of_Alzheimer'%20rel=
[Natural Products to Clear Amyloid Beta From the Brain _ Life Enhancement Products _life-enhancement.com]: https://life-enhancement.com/pages/natural-products-to-clear-amyloid-beta-from-the-brain
[Amyloid disease natural alternatives_ herbs to stop plaque _raysahelian.com]: https://www.raysahelian.com/amyloid.html
[Cannabinoids remove plaque-forming Alzheimer_s proteins from brain cells - Salk Institute for Biological Studies]: https://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/
[Sleep deprivation increases Alzheimer_s protein _ National Institutes of Health _NIH]: https://www.nih.gov/news-events/nih-research-matters/sleep-deprivation-increases-alzheimers-protein
[Staving Off Alzheimer_s Disease With The Right Diet_ Prescriptions -- ScienceDaily]: https://www.sciencedaily.com/releases/2007/11/071107211036.htm
[How to Prevent Dementia_ The Role of Cannabinoid Therapy _rxleaf.com]: https://www.rxleaf.com/how-to-prevent-dementia-thc-stops-amyloid-plaques/
[Caffeine and adenosine A_2a_ receptor antagonists prevent beta-amyloid _25-35_-induced cognitive deficits in mice - PubMed _nih.gov]: https://pubmed.ncbi.nlm.nih.gov/17007839/
[Fighting Alzheimer_s Disease_ Go for the Beta-Amyloid_ _webmd.com]: https://www.webmd.com/alzheimers/news/20001106/fighting-alzheimers-disease-go-for-beta-amyloid
[Can Alzheimer_s be Prevented_ _ Alzheimer_s Association]: https://www.alz.org/alzheimers-dementia/research_progress/prevention
[7 Tips to Reduce Amyloid Proteins in Your Brain _zoomhealth.net]: http://www.zoomhealth.net/7TipstoReduceAmyloidProteinsinYourBrain.html
[Clear Your Brain of the Toxic Gunk that Causes Alzheimer_s Disease_ _ Us Smart Publications _smart-publications.com]: https://smart-publications.com/articles/clear-your-brain-of-the-toxic-gunk-that-causes-alzheimers-disease1/
[7 Best Herbs and Spices for Brain Health _verywellmind.com]: https://www.verywellmind.com/best-herbs-and-spices-for-brain-health-4047818
[Nat Commun_A_42_40_a_ _qq.com]: https://xw.qq.com/cmsid/20200406A0NO1E00
[19 _ _A_40_A_42_ - _ _zhihu.com]: https://www.zhihu.com/question/325607785/answer/699159029
[Acta Neuropathologica_AD_ _-_ - _ _zhihu.com]: https://zhuanlan.zhihu.com/p/259620132
[Nat_Commun_A_ - _ - _ _bioon.com]: https://www.bioon.com/article/6758199.html
[-_ _xinhuanet.com]: http://www.xinhuanet.com/2021-02/03/c_1127060775.htm
[Curcuminoids enhance amyloid-_ uptake by macrophages of Alzheimer_s disease patients - IOS Press]: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad00606#:~:text=The%20natural%20product%20curcuminoids%20enhanced%20brain%20clearance%20of,measured%20A%CE%B2%20uptake%20using%20fluorescence%20and%20confocal%20microscopy.
[Curcuminoids in neurodegenerative diseases - PubMed _nih.gov]: https://pubmed.ncbi.nlm.nih.gov/22742420/
[Deceptive curcumin offers cautionary tale for chemists _ Nature]: https://www.nature.com/articles/541144a
[Don_t discount all curcumin trial data _ Nature]: https://www.nature.com/articles/543040c
[_medlive.cn]: https://news.medlive.cn/all/info-progress/show-43710_100.html