López O L, DeKosky S T
Departamento de Neurología, Facultad de Medicina, Universidad de Pittsburgh, Pittsburgh, PA 15213, USA.
Rev Neurol. 2003;37(2):155-63.
The neuropathological hallmarks of Alzheimer s disease (AD) are the presence of senile (neuritic) plaques (NP), neurofibrillary tangles (NFT), synapse loss, and neuronal cell loss. Large neurons are more affected than small ones. AD patients can also have other non specific lesions, such as granulovacuolar degeneration, Hirano bodies, and Lewy bodies. AD patients present a loss of many cholinergic neurons, especially those located in the nucleus basalis of Meynert, as well as a decrease of choline acetyl transferase (ChAT) activity, which suggested that the core of the cognitive deficits of AD was caused by the loss of cholinergic input. Interestingly, recent studies conducted in subjects with mild cognitive impairment (MCI) (these are patients that are at risk of developing AD) have shown that these subjects can have NP and NFT in the neocortex and allocortex, with relatively normal levels of ChAT in a variety of brain regions. This suggests the structures of the cholinergic system are preserved in early stages of the disease. Scientists have made significant advances in understanding both the clinical manifestations and pathobiological manifestations of AD. However, the mechanisms of specific vulnerability of the cholinergic system to AD, as well as the initial process that leads to the complex neuropathological lesions are unknown.
阿尔茨海默病（AD）的神经病理学特征包括老年斑（神经炎性斑，NP）、神经原纤维缠结（NFT）、突触丧失和神经元细胞丧失。大神经元比小神经元受影响更严重。AD患者还可能有其他非特异性病变，如颗粒空泡变性、 Hirano小体和路易小体。AD患者存在许多胆碱能神经元丧失，尤其是位于Meynert基底核的那些神经元，同时胆碱乙酰转移酶（ChAT）活性降低，这表明AD认知缺陷的核心是由胆碱能输入丧失所致。有趣的是，最近对轻度认知障碍（MCI）患者（这些患者有发展为AD的风险）进行的研究表明，这些患者在新皮质和异皮质中可出现NP和NFT，且在多个脑区ChAT水平相对正常。这表明胆碱能系统的结构在疾病早期得以保留。科学家们在理解AD的临床表现和病理生物学表现方面取得了重大进展。然而，胆碱能系统对AD的特异性易损机制以及导致复杂神经病理病变的初始过程尚不清楚。
