Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology

Am J Pathol. 2002 Nov;161(5):1869-79. doi: 10.1016/s0002-9440(10)64463-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / cytology
  • Brain / ultrastructure
  • Cytoplasmic Vesicles / chemistry*
  • Cytoplasmic Vesicles / ultrastructure
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Immunoelectron
  • Middle Aged
  • Neurons / chemistry*
  • Neurons / ultrastructure
  • Peptide Fragments / analysis*
  • Peptide Fragments / immunology
  • Rats
  • Synapses / chemistry
  • Synapses / ultrastructure*


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • amyloid beta-protein (1-42)