Parenchymal border macrophages regulate tau pathology and tau-mediated neurodegeneration

被引：14

作者：

Drieu, Antoine ^{[1
,5
]}

Du, Siling ^{[1
,5
]}

Kipnis, Michal ^{[2
,3
,4
]}

Bosch, Megan E. ^{[2
,3
,4
]}

Herz, Jasmin ^{[1
,5
]}

Lee, Choonghee ^{[2
,3
,4
]}

Jiang, Hong ^{[2
,3
,4
]}

Manis, Melissa ^{[2
,3
,4
]}

Ulrich, Jason D. ^{[2
,3
,4
]}

Kipnis, Jonathan ^{[1
,5
]}

Holtzman, David M. ^{[2
,3
,4
]}

Gratuze, Maud ^{[2
,3
,4
,6
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA

[2] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Ctr Brain Immunol & Glia, St Louis, MO USA

[6] Aix Marseille Univ, Inst NeuroPhysiopathol INP, UMR7051, Marseille, France

来源：

LIFE SCIENCE ALLIANCE | 2023年 / 6卷 / 11期

基金：

美国国家卫生研究院;

关键词：

PERIVASCULAR MACROPHAGES; BETA;

D O I：

10.26508/lsa.202302087

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Parenchymal border macrophages (PBMs) reside close to the central nervous system parenchyma and regulate CSF flow dynamics. We recently demonstrated that PBMs provide a clearance pathway for amyloid-& beta; peptide, which accumulates in the brain in Alzheimer's disease (AD). Given the emerging role for PBMs in AD, we explored how tau pathology affects the CSF flow and the PBM populations in the PS19 mouse model of tau pathology. We demonstrated a reduction of CSF flow, and an increase in an MHCII+PBM subpopulation in PS19 mice compared with WT littermates. Consequently, we asked whether PBM dysfunction could exacerbate tau pathology and tau-mediated neurodegeneration. Pharmacological depletion of PBMs in PS19 mice led to an increase in tau pathology and tau-dependent neurodegeneration, which was independent of gliosis or aquaporin-4 depolarization, essential for the CSF-ISF exchange. Together, our results identify PBMs as novel cellular regulators of tau pathology and tau-mediated neurodegeneration.

引用

页数：12

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