Abstract
Progressive accumulation of Amyloid-beta (A beta) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer's disease (AD). During disease progression, extracellular A beta plaques undergo specific changes in their composition by the sequential deposition of different modified A beta species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of A beta. Recent studies showed that rare variants of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with an increased risk for AD. Post-translational modifications of A beta could modulate the interaction with TREM2, and the uptake by microglia. Here, we demonstrate that genetic deletion of TREM2 or expression of a disease associated TREM2 variant in mice lead to differential accumulation of modified and non-modified A beta species in extracellular plaques and intraneuronal deposits. Human brains with rare TREM2 AD risk variants also showed altered deposition of modified A beta species in the different brain lesions as compared to cases with the common variant of TREM2. These findings indicate that TREM2 plays a critical role in the development and the composition of A beta deposits, not only in extracellular plaques, but also intraneuronally, that both could contribute to the pathogenesis of AD.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine Medicine > Munich Cluster for Systems Neurology (SyNergy) |
| Subjects: | 600 Technology > 610 Medicine and health |
| URN: | urn:nbn:de:bvb:19-epub-99301-7 |
| ISSN: | 2051-5960 |
| Language: | English |
| Item ID: | 99301 |
| Date Deposited: | 05. Jun 2023, 15:31 |
| Last Modified: | 07. Jun 2024, 11:24 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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