title: Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer's disease.
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.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. steven.arnold@uphs.upenn.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Natalia
authors.initials: N
authors.lastname: Louneva
authors.forename: Kajia
authors.initials: K
authors.lastname: Cao
authors.forename: Li-San
authors.initials: LS
authors.lastname: Wang
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Han
authors.forename: David A
authors.initials: DA
authors.lastname: Wolk
authors.forename: Selamawit
authors.initials: S
authors.lastname: Negash
authors.forename: Sue E
authors.initials: SE
authors.lastname: Leurgans
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: Aron S
authors.initials: AS
authors.lastname: Buchman
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilson
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D010751:Phosphopyruvate Hydratase; D040081:Protein Array Analysis; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure; D016875:tau Proteins / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D016875:tau Proteins; D010751:Phosphopyruvate Hydratase