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Epidemiology, pathology, and pathogenesis of Alzheimer disease

C. Dirk Keene, MD, PhD
Thomas J Montine, MD, PHD
Lewis H Kuller, MD, DrPH
Section Editor
Steven T DeKosky, MD, FAAN, FACP, FANA
Deputy Editor
April F Eichler, MD, MPH


Alzheimer disease (AD) is the most common cause of dementia and one of the leading sources of morbidity and mortality in the aging population.

The hallmark neuropathologic changes of AD are diffuse and neuritic plaques, marked by extracellular amyloid beta deposition, and neurofibrillary tangles, comprised of the intracellular accumulation of hyperphosphorylated tau (p-tau) protein. The epidemiologic study of AD is being transformed by the availability of new biomarker technologies to measure such neuropathologic changes in vivo. Large randomized clinical trials are evaluating anti-amyloid and other disease-based therapies for the treatment and prevention of AD utilizing these imaging or cerebrospinal fluid biomarkers [1].  

The epidemiologic study of AD has focused on three interrelated hypotheses [2]:

Extracellular amyloid plaques (primarily composed of amyloid beta peptides containing 42 amino acids [amyloid beta 42]) are a unique genetic and lifestyle disease due to increased production of amyloid beta 42 in younger, genetically high-risk individuals and reduced metabolism and removal among older individuals

Vascular disease is an independent determinant of vascular dementia but also of increased amyloid deposition and neurodegeneration


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