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Parhizkar, S.* ; Arzberger, T.* ; Brendel, M.* ; Kleinberger, G.* ; Deussing, M.* ; Focke, C.* ; Nuscher, B.* ; Xiong, M.* ; Ghasemigharagoz, A.* ; Katzmarski, N.* ; Krasemann, S.* ; Lichtenthaler, S.F.* ; Müller, S.A.* ; Colombo, A.* ; Monasor, L.S.* ; Tahirovic, S.* ; Herms, J.* ; Willem, M.* ; Pettkus, N.* ; Butovsky, O.* ; Bartenstein, P.* ; Edbauer, D.* ; Rominger, A.* ; Ertürk, A. ; Grathwohl, S.A.* ; Neher, J.J.* ; Holtzman, D.M.* ; Meyer-Luehmann, M.* ; Haass, C.*

Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE.

Nat. Neurosci. 22, 191-204 (2019)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with late-onset Alzheimer's disease (AD). We demonstrate that amyloid plaque seeding is increased in the absence of functional Trem2. Increased seeding is accompanied by decreased microglial clustering around newly seeded plaques and reduced plaque-associated apolipoprotein E (ApoE). Reduced ApoE deposition in plaques is also observed in brains of AD patients carrying TREM2 coding variants. Proteomic analyses and microglia depletion experiments revealed microglia as one origin of plaque-associated ApoE. Longitudinal amyloid small animal positron emission tomography demonstrates accelerated amyloidogenesis in Trem2 loss-of-function mutants at early stages, which progressed at a lower rate with aging. These findings suggest that in the absence of functional Trem2, early amyloidogenesis is accelerated due to reduced phagocytic clearance of amyloid seeds despite reduced plaque-associated ApoE.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 1097-6256
e-ISSN 1546-1726
Zeitschrift Nature Neuroscience
Quellenangaben Band: 22, Heft: 2, Seiten: 191-204 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Tissue Engineering and Regenerative Medicine (ITERM)