Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer's disease.

Growing evidence suggests that amyloid beta (Aβ) and tau pathologies are strongly associated with mitochondrial dysfunction and neuronal damage in Alzheimer's disease (AD). Extensive research of AD postmortem brains, mouse and fly models, including triple transgenic AD mice and mutant tau mice, and cell culture studies revealed that tau hyperphosphorylation is caused by multiple factors, including intraneuronal Aβ-oligomers, chronic oxidative stress, reduced insulin-like growth factor 1, and astrocytic mediated-Aβ and caspase activation. Overexpressed and phosphorylated tau appears to impair axonal transport of organelles causing synapse starvation, depletion of ATP, and ultimately neuronal damage. This article evaluates the role of tau in mitochondrial dysfunction and assesses how hyperphosphorylated tau impairs axonal transport of organelles in AD neurons.