美国国家衰老研究所-阿尔茨海默病协会对散发性阿尔茨海默病(sAD)的定义和分类是基于β-淀粉样蛋白驱动sAD发病机理的假设。因此,β-淀粉样蛋白病理学是sAD诊断的非条件。神经病理学诊断基于老年斑(SP)和神经原纤维缠结(NFT)的并发性,被指定为阿尔茨海默病神经病理学改变。然而,NFT在SP出现之前几十年在大脑中发展,它们的分布与SP的分布不平行。此外,在65岁时约有85%的个体中发现了NFT,在80岁时约有97%的个体中发现了NFT。SPs在65岁时发生在30%,在80岁时发生在50%-60%。在sAD中已经确定了70多个遗传风险因素;编码的蛋白质调节细胞膜,突触,脂质代谢,和神经炎症。阿尔茨海默病(AD)序曲为进一步讨论脑老化和sAD提供了新的概念和定义。AD序曲提出sAD是:(i)多因素和渐进的神经退行性生物学过程,(ii)以3R4RtauNFT的早期出现为特征,(iii)β-淀粉样蛋白和SP的后期沉积,(Iv)NFT和SP的区域分布特别不重叠,(v)在影响细胞膜的分子变化之前或同时发生,细胞骨架,突触,脂质和蛋白质代谢,能量代谢,神经炎症,细胞周期,星形胶质细胞,小胶质细胞,和血管;(vi)伴有进行性神经元丢失和脑萎缩,(vii)在人类大脑老化中普遍存在,和(viii)表现为临床前AD,由于AD,并没有普遍进展为轻度认知障碍,温和,中度,和严重的AD痴呆。
National Institute on Aging-Alzheimer\'s Association definition and classification of sporadic Alzheimer\'s disease (sAD) is based on the assumption that β-amyloid drives the pathogenesis of sAD, and therefore, β-amyloid pathology is the sine-qua-non condition for the diagnosis of sAD. The neuropathological diagnosis is based on the concurrence of senile plaques (SPs) and neurofibrillary tangles (NFTs) designated as Alzheimer\'s disease neuropathological changes. However, NFTs develop in the brain decades before the appearance of SPs, and their distribution does not parallel the distribution of SPs. Moreover, NFTs are found in about 85% of individuals at age 65 and around 97% at age 80. SPs occur in 30% at age 65 and 50%-60% at age 80. More than 70 genetic risk factors have been identified in sAD; the encoded proteins modulate cell membranes, synapses, lipid metabolism, and neuroinflammation. Alzheimer\'s disease (AD) overture provides a new concept and definition of brain aging and sAD for further discussion. AD overture proposes that sAD is: (i) a multifactorial and progressive neurodegenerative biological process, (ii) characterized by the early appearance of 3R + 4Rtau NFTs, (iii) later deposition of β-amyloid and SPs, (iv) with particular non-overlapped regional distribution of NFTs and SPs, (v) preceded by or occurring in parallel with molecular changes affecting cell membranes, cytoskeleton, synapses, lipid and protein metabolism, energy metabolism, neuroinflammation, cell cycle, astrocytes, microglia, and blood vessels; (vi) accompanied by progressive neuron loss and brain atrophy, (vii) prevalent in human brain aging, and (viii) manifested as pre-clinical AD, and progressing not universally to mild cognitive impairment due to AD, and mild, moderate, and severe AD dementia.