Affiliations: Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
Correspondence:
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Correspondence to: Qian Cai, Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. Tel.: +1 848 445 1633; Fax: +1 732 445 1794; E-mail: cai@biology.rutgers.edu.
Abstract: Alzheimer’s disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release. Mitochondrial abnormalities are one of the earliest and prominent features in AD patient brains. Amyloid-β (Aβ) and tau both trigger mitochondrial alterations. Accumulating evidence suggests that mitochondrial perturbation acts as a key factor that is involved in synaptic failure and degeneration in AD. The importance of mitochondria in supporting synaptic function has made them a promising target of new therapeutic strategies for AD. Here, we review the molecular mechanisms regulating mitochondrial function at synapses, highlight recent findings on the disturbance of mitochondrial dynamics and transport in AD, and discuss how these alterations impact synaptic vesicle release and thus contribute to synaptic pathology associated with AD.
Keywords: Alzheimer’s disease, amyloid-β, ATP supply, axonal transport, mitochondrial trafficking, neurotransmitter, oxidative stress, synaptic pathology, synaptic vesicle release, tau
