[A new hypothesis for early pathogenesis in Alzheimer's disease: impaired axonal transport mechanism].

Alzheimer's disease (AD) is characterized by amyloid beta (Abeta) plaques and neurofibrillary tangles in the brain, reduced synaptic density, and progressive neuronal dysfunction and loss. The elevated levels of the Abeta peptides in brain likely associated to neurodegeneration and cognitive and behavioral abnormalities. While such amyloid mechanism contributes to Alzheimer's pathological conditions, recent studies from a number of laboratories suggest that defective axonal transport may represent an early stage in AD pathogenesis because axonal swellings and reduced axonal transport were observed before apparent AD hallmarks. Here, we overview recent findings that could compromise neuronal abnormalities and provide molecular and cellular insights into the potential mechanisms underlying the defective axonal transport. We also discuss issues to be addressed in future in elucidation of the complex cellular events involved in AD pathogenesis.