The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid β-peptide (Aβ) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than Aβ plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD. A growing amount of evidence suggests that soluble Aβ oligomers in concert with hyperphosphorylated tau (pTau) serve as the major pathogenic drivers of neurodegeneration in AD. Increased Aβ oligomers trigger neuronal dysfunction and network alternations in learning and memory circuitry prior to clinical onset of AD, leading to cognitive decline. Furthermore, accumulated damage to mitochondria in the course of aging, which is the best-known nongenetic risk factor for AD, may collaborate with soluble Aβ and pTau to induce synapse loss and cognitive impairment in AD. In this review, I summarize and discuss the current knowledge of the molecular and cellular biology of AD and also the mechanisms that underlie Aβ-mediated neurodegeneration.
Keywords: APP; Alzheimer’s disease; amyloid β-peptide; neurodegeneration; tau.