Infiltrating Hematogenous Macrophages Aggregate Around β-Amyloid Plaques in an Age- and Sex-Dependent Manner in a Mouse Model of Alzheimer Disease.

Abstract:

:β-Amyloid (Aβ) 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 (mMϕ) from hematogenous macrophages (hMϕ), as they are morphologically and phenotypically similar when activated. To distinguish between mMϕ and hMϕ 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 hMϕ, but not in mMϕ. These mice were crossed with 5XFAD mice. The offspring demonstrated robust AD pathology and enabled visual discrimination of mMϕ from hMϕ. Mutant mice demonstrated robust increases in Aβ1-42, area of Aβ plaques, gliosis and deficits in spatial learning by age 5 months. The time-course of Aβ accumulation, paralleled by the accumulation of hMϕ around Aβ plaques, was more robust in female compared with male mice and preceded behavioral changes. Thus, the accumulation of infiltrating hMϕ around Aβ plaques was age- and sex-dependent and preceded cognitive impairment.

authors

Kozyrev N,Albers S,Yang J,Prado VF,Prado MAM,Fonseca GJ,Rylett RJ,Dekaban GA

doi

10.1093/jnen/nlaa093

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

1147-1162

issue

11

eissn

0022-3069

issn

1554-6578

pii

5917814

journal_volume

79

pub_type

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