title: Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory.
abstract: Alzheimer's disease (AD) and antecedent factors associated with AD were explored using amyloid imaging and unbiased measures of longitudinal atrophy in combination with reanalysis of previous metabolic and functional studies. In total, data from 764 participants were compared across five in vivo imaging methods. Convergence of effects was seen in posterior cortical regions, including posterior cingulate, retrosplenial, and lateral parietal cortex. These regions were active in default states in young adults and also showed amyloid deposition in older adults with AD. At early stages of AD progression, prominent atrophy and metabolic abnormalities emerged in these posterior cortical regions; atrophy in medial temporal regions was also observed. Event-related functional magnetic resonance imaging studies further revealed that these cortical regions are active during successful memory retrieval in young adults. One possibility is that lifetime cerebral metabolism associated with regionally specific default activity predisposes cortical regions to AD-related changes, including amyloid deposition, metabolic disruption, and atrophy. These cortical regions may be part of a network with the medial temporal lobe whose disruption contributes to memory impairment.
authors.affiliation: Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63105, USA. rbuckner@artsci.wustl.edu
authors.forename: Randy L
authors.initials: RL
authors.lastname: Buckner
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Shannon
authors.forename: Gina
authors.initials: G
authors.lastname: LaRossa
authors.forename: Rimmon
authors.initials: R
authors.lastname: Sachs
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Fotenos
authors.forename: Yvette I
authors.initials: YI
authors.lastname: Sheline
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D000682:Amyloid / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000502:physiology*; D049268:Positron-Emission Tomography; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
chemical_list: D000682:Amyloid