title: Cognitive reserve, presynaptic proteins and dementia in the elderly.
abstract: Differences in cognitive reserve may contribute to the wide range of likelihood of dementia in people with similar amounts of age-related neuropathology. The amounts and interactions of presynaptic proteins could be molecular components of cognitive reserve, contributing resistance to the expression of pathology as cognitive impairment. We carried out a prospective study with yearly assessments of N = 253 participants without dementia at study entry. Six distinct presynaptic proteins, and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25) and syntaxin, were measured in post-mortem brains. We assessed the contributions of Alzheimer's disease (AD) pathology, cerebral infarcts and presynaptic proteins to odds of dementia, level of cognitive function and cortical atrophy. Clinical dementia was present in N = 97 (38.3%), a pathologic diagnosis of AD in N = 142 (56.1%) and cerebral infarcts in N = 77 (30.4%). After accounting for AD pathology and infarcts, greater amounts of vesicle-associated membrane protein, complexins I and II and the SNAP-25/syntaxin interaction were associated with lower odds of dementia (odds ratio = 0.36-0.68, P < 0.001 to P = 0.03) and better cognitive function (P < 0.001 to P = 0.03). Greater cortical atrophy, a putative dementia biomarker, was not associated with AD pathology, but was associated with lower complexin-II (P = 0.01) and lower SNAP-25/syntaxin interaction (P < 0.001). In conclusion, greater amounts of specific presynaptic proteins and distinct protein-protein interactions may be structural or functional components of cognitive reserve that reduce the risk of dementia with aging.
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. william.honer@ubc.ca
authors: W G
authors: WG
authors: Honer
authors: A M
authors: AM
authors: Barr
authors: K
authors: K
authors: Sawada
authors: A E
authors: AE
authors: Thornton
authors: M C
authors: MC
authors: Morris
authors: S E
authors: SE
authors: Leurgans
authors: J A
authors: JA
authors: Schneider
authors: D A
authors: DA
authors: Bennett
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D058245:Cognitive Reserve / Q000502:physiology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D050765:Qa-SNARE Proteins / Q000502:physiology*; D050683:R-SNARE Proteins / Q000502:physiology; D012016:Reference Values; D018570:Risk Assessment; D013569:Synapses / Q000502:physiology*; D050825:Synaptosomal-Associated Protein 25 / Q000502:physiology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; C095992:complexin I; C095993:complexin II