Alzheimer disease: update on basic mechanisms.

Alzheimer disease is the most common form of dementia in the aged population. Pathologically, Alzheimer disease is characterized by progressive synaptic and neuronal loss and the presence of diagnostic amyloid plaques, consisting of fibril b-amyloid peptide aggregates and neurofibrillary tangles containing hyperphosphorylated tau protein filaments. Although plaques and tangles were originally considered the mediators of neurotoxicity in Alzheimer disease, recent research has underscored the roles of soluble β-amyloid oligomers and tau molecules. Furthermore, new evidence has re-emphasized the important roles of endocytic, autophagic, and lysosomal pathways in Alzheimer disease pathogenesis-including the finding that deficiency or mutations in the gene that encodes presenilin 1 (the most common cause for early-onset familial Alzheimer disease) impairs the maturation of the lysosomal proton pump. The author discusses recent developments in the perspective of Alzheimer disease pathogenesis and potential therapeutic interventions.