Ingelsson M, Fukumoto H, Newell K L, Growdon J H, Hedley-Whyte E T, Frosch M P, Albert M S, Hyman B T, Irizarry M C
Harvard Medical School, Massachusetts General Hospital, Boston.
Neurology. 2004 Mar 23;62(6):925-31. doi: 10.1212/01.wnl.0000115115.98960.37.
Pathologic changes in the Alzheimer disease (AD) brain occur in a hierarchical neuroanatomical pattern affecting cortical, subcortical, and limbic regions.
To define the time course of pathologic and biochemical changes-amyloid deposition, amyloid beta-peptide (Abeta) accumulation, neurofibrillary tangle (NFT) formation, synaptic loss, and gliosis-within the temporal association cortex of AD cases of varying disease duration, relative to control brains.
Stereologic assessments of amyloid burden and tangle density as well as ELISA-based measurements of Abeta, synaptophysin, and glial fibrillary acidic protein (GFAP) were performed in the superior temporal sulcus from a cohort of 83 AD and 26 nondemented control brains.
Relative to control cases, AD brains were characterized by accumulation of NFT and amyloid plaques, increase of tris- and formic acid-extractable Abeta species, reduced levels of synaptophysin, and elevated levels of GFAP. In AD cases, the duration of dementia correlated with the degree of tangle formation, gliosis, and synaptic loss but not with any Abeta measures. Accumulation of Abeta, measured both neuropathologically and biochemically, was markedly increased in AD brains independent of disease duration, even in cases of short duration.
These data support distinct processes in the initiation and progression of AD pathology within the temporal cortex: Deposition of Abeta reaches a "ceiling" early in the disease process, whereas NFT formation, synaptic loss, and gliosis continue throughout the course of the illness.
阿尔茨海默病（AD）大脑中的病理变化呈分层的神经解剖学模式，影响皮质、皮质下和边缘区域。
确定不同病程的AD病例颞叶联合皮质内病理和生化变化（淀粉样蛋白沉积、淀粉样β肽（Aβ）积累、神经原纤维缠结（NFT）形成、突触丧失和胶质细胞增生）的时间进程，并与对照大脑进行比较。
对83例AD患者和26例非痴呆对照者大脑的颞上沟进行淀粉样蛋白负荷和缠结密度的体视学评估，以及基于酶联免疫吸附测定法（ELISA）检测Aβ、突触素和胶质纤维酸性蛋白（GFAP）。
与对照病例相比，AD大脑的特征为NFT和淀粉样斑块积累、三氟乙酸和甲酸可提取的Aβ种类增加、突触素水平降低以及GFAP水平升高。在AD病例中，痴呆持续时间与缠结形成、胶质细胞增生和突触丧失程度相关，但与任何Aβ检测指标无关。无论是通过神经病理学还是生物化学方法检测，Aβ的积累在AD大脑中均显著增加，且与疾病持续时间无关，即使是病程较短的病例也是如此。
这些数据支持AD病理在颞叶皮质起始和进展过程中的不同过程：Aβ沉积在疾病过程早期达到“上限”，而NFT形成、突触丧失和胶质细胞增生在疾病全过程中持续存在。
