Cellular,synaptic, and biochemical features of resilient cognition in Alzheimer's disease |
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Authors: | Steven E. Arnold Natalia Louneva Kajia Cao Li-San Wang Li-Ying Han David A. Wolk Selamawit Negash Sue E. Leurgans Julie A. Schneider Aron S. Buchman Robert S. Wilson David A. Bennett |
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Affiliation: | 1. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA;2. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA;3. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA;4. Rush Alzheimer''s Disease Center, Rush University, Chicago, IL, USA |
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Abstract: | 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. |
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Keywords: | Cognitive reserve Synapse Synaptophysin Synaptopodin Glial fibrillary acidic protein Antibody microarray |
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