Absence of microglia or presence of peripherally‐derived macrophages does not affect tau pathology in young or old hTau mice. Issue 7 (10th February 2020)

• Record Type: Journal Article
• Authors: Zhu, Keying; Pieber, Melanie; Han, Jinming; Blomgren, Klas; Zhang, Xing‐Mei; Harris, Robert A.; Lund, Harald
• Is Part Of: Glia. Volume 68:Issue 7(2020)
• Page Start: 1466
• Page End: 1478
• Publication Date: 2020-02-10
• Subjects: Alzheimer's disease -- macrophage -- microglia -- tau; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23794
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Microglia are implicated in the pathophysiology of several neurodegenerative disorders, including Alzheimer's disease. While the role of microglia and peripheral macrophages in regulating amyloid beta pathology has been well characterized, the impact of these distinct cell subsets on tau pathology remains poorly understood. We and others have recently demonstrated that monocytes can engraft the brain and give rise to long‐lived parenchymal macrophages, even under nonpathological conditions. We undertook the current study to investigate the regulation of tau pathology by microglia and peripheral macrophages using hTau transgenic mice, which do not exhibit microglial activation/pathology or macrophage engraftment. To assess the direct impact of microglia on tau pathology we developed a protocol for long‐term microglial depletion in Cx3cr1 CreER R26 DTA mice and crossed them with hTau mice. We then depleted microglia up to 3 months in both young and old mice, but no net change in forebrain soluble oligomeric tau or total or phosphorylated levels of aggregated tau was recorded. To investigate the consequence of peripherally‐derived parenchymal macrophages on tau aggregation we partially repopulated the hTau microglial pool with peripheral macrophages, but this also did not affect levels of tau oligomers or insoluble aggregates. Our study questions the direct involvement of microglia or peripheral macrophages in the development of tau pathology in the hTau model. Abstract : Microglia remain homeostatic throughout the lifespan of hTau mice Long‐term microglia depletion does not alter tau pathology in hTau mice Long‐term engraftment of peripherally‐derived macrophages does not alter tau pathology in hTau mice