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Mitochondria and Mitochondrial Cascades in Alzheimer’s Disease

2017; IOS Press; Volume: 62; Issue: 3 Linguagem: Inglês

10.3233/jad-170585

1875-8908

Russell H. Swerdlow,

Tryptophan and brain disorders

Decades of research indicate mitochondria from Alzheimer's disease (AD) patients differ from those of non-AD individuals.Initial studies revealed structural differences, and subsequent studies showed functional deficits.Observations of structure and function changes prompted investigators to consider the consequences, significance, and causes of AD-related mitochondrial dysfunction.Currently, extensive research argues mitochondria may mediate, drive, or contribute to a variety of AD pathologies.The perceived significance of these mitochondrial changes continues to grow, and many currently believe AD mitochondrial dysfunction represents a reasonable therapeutic target.Debate continues over the origin of AD mitochondrial changes.Some argue amyloid-␤ (A␤) induces AD mitochondrial dysfunction, a view that does not challenge the amyloid cascade hypothesis and that may in fact help explain that hypothesis.Alternatively, data indicate mitochondrial dysfunction exists independent of A␤, potentially lies upstream of A␤ deposition, and suggest a primary mitochondrial cascade hypothesis that assumes mitochondrial pathology hierarchically supersedes A␤ pathology.Mitochondria, therefore, appear at least to mediate or possibly even initiate pathologic molecular cascades in AD.This review considers studies and data that inform this area of AD research.