TREM2 modulates differential deposition of modified and non-modified Aß species in extracellular plaques and intraneuronal deposits.
Acta Neuropathol Commun
; 9(1): 168, 2021 10 18.
Article
en En
| MEDLINE
| ID: mdl-34663480
ABSTRACT
Progressive accumulation of Amyloid-ß (Aß) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer's disease (AD). During disease progression, extracellular Aß plaques undergo specific changes in their composition by the sequential deposition of different modified Aß species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of Aß. 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 Aß 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 Aß species in extracellular plaques and intraneuronal deposits. Human brains with rare TREM2 AD risk variants also showed altered deposition of modified Aß 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 Aß deposits, not only in extracellular plaques, but also intraneuronally, that both could contribute to the pathogenesis of AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
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Receptores Inmunológicos
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Péptidos beta-Amiloides
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Placa Amiloide
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Enfermedad de Alzheimer
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Neuronas
Límite:
Aged
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Aged80
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Acta Neuropathol Commun
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania