Affiliations: [a] Center for Alzheimer's Disease and Related Disorders, Southern Illinois University School of Medicine, Carbondale, IL, USA | [b] Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA | [c] Department of Neurology and Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Carbondale, IL, USA | [d] Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, USA
Correspondence:
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Correspondence to: Robert G. Struble, Center for Alzheimer's Disease and Related Disorders, PO Box 19628, Southern Illinois University School of Medicine, Springfield, IL 62794, USA. Tel.: +1 217 545 4429; Fax: +1 217 545 1903; E-mail: [email protected].
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.
