Lysosomal LAMP1 immunoreactivity exists in both diffuse and neuritic amyloid plaques in the human hippocampus

Sofia Hassiotis, Jim Manavis, Peter C. Blumbergs, Kathryn Hattersley, Julian M. Carosi, Makoto Kamei, Timothy Sargeant

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Lysosomal vesicles around neuritic plaques are thought to drive Alzheimer's disease by providing ideal microenvironments for generation of amyloid-β. Although lysosomal vesicles are present at every amyloid plaque in mouse models of Alzheimer's disease, the number of amyloid plaques that contain lysosomal vesicles in the human brain remains unknown. This study aimed to quantify lysosomal vesicles at amyloid plaques in the human hippocampus. Lysosome-associated membrane protein 1 (LAMP1)-positive vesicles accumulated in both diffuse (Aβ42-positive/AT8-negative) and neuritic (Aβ42-positive/AT8-positive) plaques in all regions were analysed. In contrast to mouse models of Alzheimer's disease, however, not all amyloid plaques accumulated LAMP1-positive lysosomal vesicles. Even at neuritic plaques, LAMP1 immunoreactivity was more abundant than phospho-tau (AT8). Further, lysosomal vesicles colocalised weakly with phospho-tau such that accumulation of lysosomal vesicles and phospho-tau appeared to be spatially distinct events that occurred within dystrophic neurites. This quantitative study shows that diffuse plaques, as well as neuritic plaques, contain LAMP1 immunoreactivity in the human hippocampus.

Original languageEnglish
Pages (from-to)1043-1053
Number of pages11
JournalEuropean Journal of Neuroscience
Volume47
Issue number9
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • Alzheimer's disease
  • amyloid plaque
  • amyloid-β
  • lysosome
  • tau

ASJC Scopus subject areas

  • Neuroscience(all)

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