The Alzheimer's disease mitochondrial cascade hypothesis: an update.
In 2004 we proposed the mitochondrial cascade hypothesis of sporadic Alzheimer's disease (AD). Our hypothesis assumed sporadic and autosomal dominant AD are not etiologically homogeneous, considered evidence that AD pathology is not brain-limited, and incorporated aging theory. The mitochondrial cascade hypothesis asserted: (1) inheritance determines mitochondrial baseline function and durability; (2) mitochondrial durability influences how mitochondria change with age; and (3) when mitochondrial change reaches a threshold, AD histopathology and symptoms ensue. We now review the reasoning used to formulate the hypothesis, discuss pertinent interim data, and update its tenants. Readers are invited to consider the conceptual strengths and weaknesses of this hypothesis.
Swerdlow
Russell H
RH
Department of Neurology, University of Kansas School of Medicine, Kansas City, USA. rswerdlow@kumc.edu
Khan
Shaharyar M
SM
D000375:Aging; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins