Amyloid plaques and neurofibrillary tangles (NFTs) in the brain are the neuropathological hallmarks of Alzheimer's disease (AD). Amyloid plaques are composed of beta-amyloid peptides (A beta), while NFTs contain hyperphosphorylated tau proteins. Patients with familial AD who have mutations in the amyloid precursor protein (APP) gene have either increased production of A beta or generate more aggregation-prone forms of A beta. The findings of familial AD mutations in the APP gene suggest that A beta plays a central role in the pathophysiology of AD. A beta 42, composed of 42 amino acid residues, aggregates readily and is considered to form amyloid plaque. However, the processes of plaque formation are still not well known. It is generally thought that A beta is secreted into the extracellular space and aggregates to form amyloid plaques. A beta as extracellular aggregates and amyloid plaques are thought to be toxic to the surrounding neurons. The intraneuronal accumulation of A beta has more recently been demonstrated and is reported to be involved in synaptic dysfunction, cognitive impairment, and the formation of amyloid plaques in AD. We herein provide an overview of the process of the intraneuronal accumulation of A beta and plaque formation, and discuss its implications for the pathology, early diagnosis, and therapy of AD.