THE DISTRIBUTION OF TANGLES, PLAQUES AND RELATED IMMUNOHISTOCHEMICAL MARKERS IN HEALTHY AGING AND ALZHEIMERS-DISEASE
THE DISTRIBUTION OF TANGLES, PLAQUES AND RELATED IMMUNOHISTOCHEMICAL MARKERS IN HEALTHY AGING AND ALZHEIMERS-DISEASE
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DOI：
10.1016/0197-4580(91)90006-6
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发表时间：
1991-07-01
影响因子：
4.2
通讯作者：
WHITE, DL
中科院分区：
文献类型：
--
作者：
PRICE, JL;DAVIS, PB;WHITE, DL
神经纤维缠结和老年斑，连同细胞免疫反应的Alz-50抗体（A50-IR细胞）或抗体对成对的螺旋丝（PHF-IR细胞），和淀粉样蛋白沉积物染色的抗体对β-（或A4）-淀粉样蛋白，已被映射到整个腹侧前脑的25个老人。每个人的认知状态进行了评估，并分配了“临床痴呆评级”（CDR），无论是在华盛顿大学的记忆和衰老项目死亡前，或通过尸检采访，与适当的间接来源。研究的病例包括13例非痴呆病例（CDR = 0），6例极轻度至轻度痴呆病例（CDR = 0/0.5至1）和6例更严重的痴呆病例（CDR = 2至3）。因为即使是非常轻微的痴呆症患者的大脑也显示出实质性的病理变化，所以重点放在检查非痴呆症患者的早期变化上，这些变化可能与阿尔茨海默病有关。发现缠结和斑块的分布不同。缠结（和A50-ir和PHF-ir细胞）存在于所有检查的大脑中。在年轻的非痴呆病例（54至63岁）中，前嗅核和海马旁回有少数受累细胞。在年龄较大的非痴呆病例（73-89岁）中，在相同的区域发现了更多的缠结，并且在海马CA 1区也发现了缠结。非常轻度的痴呆病例有更多的缠结，但它们的分布相似。只有在严重痴呆的病例中，新皮层中才出现大量的缠结。相比之下，没有斑块（或β-淀粉样蛋白免疫反应性）中发现的任何年轻的非痴呆症的情况下，或在四个老年非痴呆症的情况下。在三个年龄较大的非痴呆病例中，有一些原始斑块，仅限于新皮层的局部区域（例如，下颞叶皮层的一部分）。在一个非痴呆病例和所有非常轻度到轻度痴呆病例中，都有大量的原始斑块，特别是在新皮层。随着痴呆的严重程度增加，斑块从原始向成熟转变。这些结果被解释为意味着缠结和斑块的首次发展发生在大脑的不同部位。老化期间，前嗅核、海马旁回和海马会出现缠结，但除了痴呆症的大脑之外，新皮质中很少出现缠结。相反，斑块可能首先在新皮层中发展。与缠结不同，斑块不是衰老的一贯特征，至少在80岁之前是如此。
Neurofibrillary tangles and senile plaques, together with cells immunoreactive for the Alz-50 antibody (A50-ir cells) or for an antibody against paired helical filaments (PHF-ir cells), and amyloid deposits stained with antibodies against beta-(or A4)-amyloid, have been mapped throughout the ventral forebrains of 25 old people. The cognitive status of each individual was assessed and a "Clinical Dementia Rating" (CDR) assigned, either before death in the Memory and Aging Project of Washington University, or by a postmortem interview, with an appropriate collateral source. The cases studied included 13 nondemented cases (CDR = 0), six very mildly to mildly demented cases (CDR = 0/0.5 to 1) and six more severely demented cases (CDR = 2 to 3). Because even the very mildly demented brains showed substantial pathological change, emphasis was placed on examining the nondemented cases for the earliest changes that could be associated with Alzheimer's disease. Different distributions were found for tangles and plaques. Tangles (and A50-ir and PHF-ir cells) were present in all of the brains examined. In the younger nondemented cases (aged 54 to 63) there were a few affected cells in the anterior olfactory nucleus and the parahippocampal gyrus. In older nondemented cases (aged 73-89) more tangles were found in the same areas, and also in hippocampal field CA1. The very mildly demented cases had many more tangles, but their distribution was similar. Only in the severely demented cases were large numbers of tangles present in the neocortex. In contrast, no plaques (or beta-amyloid immunoreactivity) were found in any of the younger nondemented cases or in four of the eight older nondemented cases. In three older nondemented cases there were a few primitive plaques, which were restricted to localized regions of the neocortex (e.g., a portion of the inferior temporal cortex). In one nondemented case and all of the very mildly to mildly demented cases there were very large numbers of mostly primitive plaques, particularly in the neocortex. With greater severity of dementia there is a shift from primitive to mature plaques. These results were interpreted to imply that the first development of tangles and plaques occurs in different parts of the brain. Tangles appear during aging in the anterior olfactory nucleus, the parahippocampal gyrus and the hippocampus, but are rare in the neocortex except in demented brains. Conversely plaques may develop first in the neocortex. Unlike tangles, plaques are not a consistent feature of aging, at least up to age 80.