title: Plaque formation and the intraneuronal accumulation of β-amyloid in Alzheimer's disease.
abstract: Amyloid plaques and neurofibrillary tangles (NFTs) in the brain are the neuropathological hallmarks of Alzheimer's disease (AD). Amyloid plaques are composed of β-amyloid peptides (Aβ), 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 Aβ or generate more aggregation-prone forms of Aβ. The findings of familial AD mutations in the APP gene suggest that Aβ plays a central role in the pathophysiology of AD. Aβ42, 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 Aβ is secreted into the extracellular space and aggregates to form amyloid plaques. Aβ as extracellular aggregates and amyloid plaques are thought to be toxic to the surrounding neurons. The intraneuronal accumulation of Aβ 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 Aβ and plaque formation, and discuss its implications for the pathology, early diagnosis, and therapy of AD.
authors.affiliation: Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Reisuke H
authors.initials: RH
authors.lastname: Takahashi
authors.affiliation: Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nagao
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Gunnar K
authors.initials: GK
authors.lastname: Gouras
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor
keywords: Alzheimer's disease; intraneuronal accumulation; multivesicular body; synapse; β-amyloid