The pathological presentation of Alzheimer disease (AD), the leading cause of senile dementia, involves regionalized neuronal death and an accumulation of intraneuronal and extracellular filaments termed neurofibrillary tangles and senile plaques, respectively. One of the ?-amyloid peptides (A?), the A?1-42 form, is primarily responsible for neuronal damage and cell death that is the main component in the senile plaques. Over the past twenty years, the amyloid hypothesis has been strongly supported by a wealth of evidence, including data from genetic studies of Alzheimer disease. Amyloid cascade hypothesis states that the accumulation and deposition of fibrillar A? is the primary driver of neurodegeneration and cognitive decline leading to dementia. AD is a clinicopathological syndrome in which different gene defects can lead--directly or indirectly--to alter APP expression or proteolytic processing as such to change A? stability or aggregation. These result in a chronic imbalance between A? production and clearance. Gradual accumulation of aggregated A? initiates a complex, multistep cascade that includes gliosis, inflammatory changes, neuritic/synaptic change, tangles and transmitter loss. The evidence that links A? to the pathogenesis of AD is substantial, but the means by which these peptides exert their toxic effects, and where in neuronal cells they act, is far from clear. The up-to-date proceeding in the molecular mechanism of ?-amyloid peptides is overviewed.