Are mitochondria critical in the pathogenesis of Alzheimer's disease?
This review summarizes recent findings that suggest a causal connection between mitochondrial abnormalities and sporadic Alzheimer's disease (AD). Genetic causes of AD are known only for a small proportion of familial AD patients, but for a majority of sporadic AD patients, genetic causal factors are still unknown. Currently, there are no early detectable biomarkers for sporadic AD, and there is a lack of understanding of the pathophysiology of the disease. Findings from recent genetic studies of AD pathogenesis suggest that mitochondrial defects may play an important role in sporadic AD progression, and that mitochondrial abnormalities and oxidative damage may play a significant role in the progression of familial AD. Findings from biochemical studies, in vitro studies, gene expression studies, and animal model studies of AD are reviewed, and the possible contribution of mitochondrial mutations to late-onset sporadic AD is discussed.
Reddy
P Hemachandra
PH
Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. reddyh@ohsu.edu
Beal
M Flint
MF
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D013569:Synapses / Q000502:physiology