Infiltrating Hematogenous Macrophages Aggregate Around ß-Amyloid Plaques in an Age- and Sex-Dependent Manner in a Mouse Model of Alzheimer Disease.
J Neuropathol Exp Neurol
; 79(11): 1147-1162, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-33011810
ABSTRACT
ß-Amyloid (Aß) plaques can trigger chronic inflammation in the cellular environment that recruits infiltrating macrophages during the course of Alzheimer disease (AD). Activated macrophages release pro-inflammatory cytokines that increase neurotoxicity associated with AD. A major impediment to investigating neuroinflammation involving macrophage activity is the inability to discriminate resident microglial macrophages (mMÏ) from hematogenous macrophages (hMÏ), as they are morphologically and phenotypically similar when activated. To distinguish between mMÏ and hMÏ and to determine their respective roles in chronic inflammation associated with the progression of amyloidosis, we used lys-EGFP-ki transgenic mice that express enhanced green fluorescent protein in hMÏ, but not in mMÏ. These mice were crossed with 5XFAD mice. The offspring demonstrated robust AD pathology and enabled visual discrimination of mMÏ from hMÏ. Mutant mice demonstrated robust increases in Aß1-42, area of Aß plaques, gliosis and deficits in spatial learning by age 5 months. The time-course of Aß accumulation, paralleled by the accumulation of hMÏ around Aß plaques, was more robust in female compared with male mice and preceded behavioral changes. Thus, the accumulation of infiltrating hMÏ around Aß plaques was age- and sex-dependent and preceded cognitive impairment.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Placa Amiloide
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Doença de Alzheimer
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Macrófagos
Limite:
Animals
Idioma:
En
Revista:
J Neuropathol Exp Neurol
Ano de publicação:
2020
Tipo de documento:
Article