title: Is brain amyloid production a cause or a result of dementia of the Alzheimer's type?
abstract: The amyloid cascade hypothesis has guided much of the research into Alzheimer's disease (AD) over the last 25 years. We argue that the hypothesis of amyloid-β (Aβ) as the primary cause of dementia may not be fully correct. Rather, we propose that decline in brain metabolic activity, which is tightly linked to synaptic activity, actually underlies both the cognitive decline in AD and the deposition of Aβ. Aβ may further exacerbate metabolic decline and result in a downward spiral of cognitive function, leading to dementia. This novel interpretation can tie the disparate risk factors for dementia to a unifying hypothesis and present a roadmap for interventions to decrease the prevalence of dementia in the elderly population.
authors.affiliation: Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Carbondale, IL 62794, USA. rstruble@siumed.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Struble
authors.forename: Tom
authors.initials: T
authors.lastname: Ala
authors.forename: Peter R
authors.initials: PR
authors.lastname: Patrylo
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Brewer
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Yan
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology; D006801:Humans; D012307:Risk Factors
chemical_list: D000682:Amyloid