Alzheimer's disease is not "brain aging": neuropathological, genetic, and epidemiological human studies.
Alzheimer's disease is not "brain aging": neuropathological, genetic, and epidemiological human studies.
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DOI：
10.1007/s00401-011-0826-y
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发表时间：
2011-05
影响因子：
12.7
通讯作者：
Scheff SW
中科院分区：
文献类型：
--
作者：
Nelson PT;Head E;Schmitt FA;Davis PR;Neltner JH;Jicha GA;Abner EL;Smith CD;Van Eldik LJ;Kryscio RJ;Scheff SW
人类研究回顾了“衰老”相关机制是否导致阿尔茨海默病（AD）发病机制。 AD 由特定的神经病理学定义：神经炎性淀粉样斑块和新皮质神经原纤维缠结。 AD 病理学是由与衰老本身无关的遗传因素驱动的，而是与淀粉样前体蛋白 (APP) 相关。与参与 APP 相关机制的基因相比，与人类“加速衰老”疾病（早衰症）和 AD 相关的基因之间没有牢固的联系。鉴于大多数国家的尸检率较低，老年 AD 的流行病学具有高度相关性，但解决起来却极具挑战性。在高龄时，AD 以外的脑部疾病的患病率与 AD 大致相同，而 AD 病理学的影响似乎在 95 岁时达到顶峰，此后逐渐下降。除 AD 之外，许多不同的脑部疾病都会影响老年人的大脑并导致认知障碍。其他常见的疾病包括脑血管疾病和海马硬化症，这两种脑部疾病的发病率都很高，按时间顺序来看，发病率高峰似乎晚于 AD。由于这些高龄常见脑部疾病，临床“痴呆”和具有 AD 病理学的痴呆病例子集之间的流行病学有所不同。其他与衰老相关的认知能力下降机制（例如糖尿病和突触丧失）已与 AD 相关，并且对这些假设进行了讨论。提出了定义“与衰老相关”疾病的标准，而 AD 不符合所有这些标准。总之，将注意力集中在 AD 所涉及的特定途径上，而不是将其归因于衰老的不可避免的后果，可能是最有成效的。
Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging.
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影响因子：
4.2
作者：
Ball, M;Braak, H;Khachaturian, Z
通讯作者：
Khachaturian, Z
影响因子：
9.9
作者：
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通讯作者：
HYMAN, BT
影响因子：
9.9
作者：
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通讯作者：
Frey, WH
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5.7
作者：
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通讯作者：
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影响因子：
9.9
作者：
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通讯作者：
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