Fig. 1

Critical role of mitochondrial dysfunction in AD. Mitochondrial dysfunction plays a critical role in AD either as a primary or secondary event. In either case, impaired mitochondrial bioenergetics, increased oxidative stress and disturbed mitochondrial genome are consistent features of mitochondrial abnormalities in AD, all which interact with each other to form a deleterious downward spiral. While the relative importance of these abnormalities in triggering mitochondrial dysfunction may vary among patients with AD depending on the unique biological, environmental and genetic factors of each individual, any of these abnormalities could induce the other two to complete the downward spiral to mediate and amplify neuronal dysfunction and neurodegeneration. Recent studies revealed mechanisms underlying the loss of integrity of mitochondria, which provides mechanistic link among these abnormalities and offers multiple novel intervention sites to improve mitochondrial function in AD