CCL2 Overexpression in the Brain Promotes Glial Activation and Accelerates Tau Pathology in a Mouse Model of Tauopathy.

Frontiers in Immunology
Aurelie Joly-AmadoMaj-Linda B Selenica

Abstract

Innate immune activation is a major contributor to Alzheimer's Disease (AD) pathophysiology, although the mechanisms involved are poorly understood. Chemokine C-C motif ligand (CCL) 2 is produced by neurons and glial cells and is upregulated in the AD brain. Transgene expression of CCL2 in mouse models of amyloidosis produces microglia-induced amyloid β oligomerization, a strong indication of the role of these activation pathways in the amyloidogenic processes of AD. We have previously shown that CCL2 polarizes microglia in wild type mice. However, how CCL2 signaling contributes to tau pathogenesis remains unknown. To address this question, CCL2 was delivered via recombinant adeno-associated virus serotype 9 into both cortex and hippocampus of a mouse model with tau pathology (rTg4510). We report that CCL2 overexpression aggravated tau pathology in rTg4510 as shown by the increase in Gallyas stained neurofibrillary tangles as well as phosphorylated tau-positive inclusions. In addition, biochemical analysis showed a reduction in the levels of detergent-soluble tau species followed by increase in the insoluble fraction, indicating a shift toward larger tau aggregates. Indeed, increased levels of high molecular weight species of p...Continue Reading

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Citations

Dec 21, 2020·Clinical Neurology and Neurosurgery·Haili WangYingzhu Chen
Dec 19, 2020·Biomedicines·Natalia RybtsovaStanislav Rybtsov
Jul 3, 2021·Frontiers in Aging Neuroscience·Sanghamitra Bandyopadhyay
Jul 9, 2021·International Immunopharmacology·Sanjiv SinghV Ravichandiran
Jan 9, 2022·Alzheimer's Research & Therapy·Juan Luis Sanchez-SanchezUNKNOWN MAPT/DSA Group

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Methods Mentioned

BETA
PCR
fluorescence imaging
protein assay
transgenic
genotyping

Software Mentioned

Elements AR
Fiji
ImageJ
AlphaEase
GraphPad
Nearcyte
GraphPad Prism
NIS
Sholl

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