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

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dc.contributor.authorHassiotis, S.
dc.contributor.authorManavis, J.
dc.contributor.authorBlumbergs, P.C.
dc.contributor.authorHattersley, K.J.
dc.contributor.authorCarosi, J.M.
dc.contributor.authorKamei, M.
dc.contributor.authorSargeant, T.J.
dc.date.issued2018
dc.description.abstractLysosomal 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.
dc.description.statementofresponsibilitySofia Hassiotis, Jim Manavis, Peter C. Blumbergs, Kathryn J. Hattersley, Julian M. Carosi, Makoto Kamei, and Timothy J. Sargeant
dc.identifier.citationEuropean Journal of Neuroscience, 2018; 47(9):1043-1053
dc.identifier.doi10.1111/ejn.13913
dc.identifier.issn0953-816X
dc.identifier.issn1460-9568
dc.identifier.orcidManavis, J. [0000-0001-7381-7781] [0000-0003-1268-561X]
dc.identifier.orcidCarosi, J.M. [0000-0001-6820-3953]
dc.identifier.orcidKamei, M. [0000-0002-1438-0783]
dc.identifier.orcidSargeant, T.J. [0000-0003-1254-4390]
dc.identifier.urihttp://hdl.handle.net/2440/121286
dc.language.isoen
dc.publisherWiley
dc.rights© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
dc.source.urihttps://doi.org/10.1111/ejn.13913
dc.subjectAlzheimer's disease
dc.subjectamyloid plaque
dc.subjectamyloid-β
dc.subjectlysosome
dc.subjecttau
dc.titleLysosomal LAMP1 immunoreactivity exists in both diffuse and neuritic amyloid plaques in the human hippocampus
dc.typeJournal article
pubs.publication-statusPublished

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