Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer's disease.
J Neurosci
; 31(31): 11159-71, 2011 Aug 03.
Article
en En
| MEDLINE
| ID: mdl-21813677
ABSTRACT
Mononuclear phagocytes are important modulators of Alzheimer's disease (AD), but the specific functions of resident microglia, bone marrow-derived mononuclear cells, and perivascular macrophages have not been resolved. To elucidate the spatiotemporal roles of mononuclear phagocytes during disease, we targeted myeloid cell subsets from different compartments and examined disease pathogenesis in three different mouse models of AD (APP(swe/PS1), APP(swe), and APP23 mice). We identified chemokine receptor 2 (CCR2)-expressing myeloid cells as the population that was preferentially recruited to ß-amyloid (Aß) deposits. Unexpectedly, AD brains with dysfunctional microglia and devoid of parenchymal bone marrow-derived phagocytes did not show overt changes in plaque pathology and Aß load. In contrast, restriction of CCR2 deficiency to perivascular myeloid cells drastically impaired ß-amyloid clearance and amplified vascular Aß deposition, while parenchymal plaque deposition remained unaffected. Together, our data advocate selective functions of CCR2-expressing myeloid subsets, which could be targeted specifically to modify disease burden in AD.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
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Microglía
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Células Mieloides
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Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania