References
Query Results -- Details
MGI Accession ID: MGI:2389553
J Number: J:79908
Other Accession IDs:
Title: Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology.
Authors: Takahashi RH; Milner TA; Li F; Nam EE; Edgar MA; Yamaguchi H; Beal MF; Xu H; Greengard P; Gouras GK
Journal: Am J Pathol
Volume: 161
Issue: 5
Date: 2002 Nov
Year: 2002
Pages: 1869-79
Review Status: Peer Reviewed
Abstract:
A central question in Alzheimer's disease concerns the mechanism by which beta-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular beta-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as beta-amyloid levels rise, months before the appearance of beta-amyloid plaques. We have now used immunoelectron microscopy to determine the subcellular site of neuronal beta-amyloid in normal and Alzheimer brains, and in brains from Alzheimer transgenic mice. We report that beta-amyloid 42 localized predominantly to multivesicular bodies of neurons in normal mouse, rat, and human brain. In transgenic mice and human Alzheimer brain, intraneuronal beta-amyloid 42 increased with aging and beta-amyloid 42 accumulated in multivesicular bodies within presynaptic and especially postsynaptic compartments. This accumulation was associated with abnormal synaptic morphology, before beta-amyloid plaque pathology, suggesting that intracellular accumulation of beta-amyloid plays a crucial role in Alzheimer's disease.
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