Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Neurobiol Aging. 2013 Jan;34(1):157-68. doi: 10.1016/j.neurobiolaging.2012.03.004. Epub 2012 May 2.
Although neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect, as some people exhibit normal cognition despite high levels of Alzheimer's disease (AD) pathology. We compared the cellular, synaptic, and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: (1) pathological AD with normal cognition ("AD-Resilient"), (2) pathological AD with AD-typical dementia ("AD-Dementia"), and (3) pathologically normal with normal cognition ("Normal Comparison"). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared with the AD-Dementia group, and increased densities of glial fibrillary acidic protein astrocytes compared with both the AD-Dementia and Normal Comparison groups. Further, in a discovery-type antibody microarray protein analysis, we identified a number of candidate protein abnormalities that were associated with a particular diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD.
尽管老年人大脑中的神经原纤维缠结和神经纤维缠结与认知障碍和痴呆严重程度相关，但长期以来人们一直认识到，这种关系并不完美，因为有些人尽管存在高水平的阿尔茨海默病（AD）病理，但表现出正常的认知能力。我们比较了宗教秩序研究中女性受试者的额中皮质的细胞、突触和生化组成，这些女性受试者分为三个亚组：（1）认知正常的病理性 AD（“AD 有韧性”），（2）认知正常的病理性 AD 与 AD 典型痴呆（“AD 痴呆”），以及（3）认知正常的病理性正常（“正常比较”）。与 AD 痴呆组相比，AD 有韧性组的突触小泡素标记的突触前末端和突触后蛋白素标记的树突棘密度保持不变，与 AD 痴呆组和正常比较组相比，胶质纤维酸性蛋白星形胶质细胞的密度增加。此外，在发现型抗体微阵列蛋白质分析中，我们确定了一些候选蛋白异常，这些异常与特定的诊断组相关。这些数据描述了细胞和突触特征，并确定了可能与病理性 AD 认知大脑老化有韧性相关的新的生化靶标。
