Please use this identifier to cite or link to this item: doi:10.22028/D291-34610
Title: Haploinsufficiency of microglial MyD88 ameliorates Alzheimer's pathology and vascular disorders in APP/PS1-transgenic mice
Author(s): Quan, Wenqiang
Luo, Qinghua
Hao, Wenlin
Tomic, Inge
Furihata, Tomomi
Schulz-Schäffer, Walter
Menger, Michael D.
Fassbender, Klaus
Liu, Yang
Language: English
Title: Glia
Volume: 69
Issue: 8
Pages: 1987-2005
Publisher/Platform: Wiley
Year of Publication: 2021
Free key words: Alzheimer's disease
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Growing evidence indicates that innate immune molecules regulate microglial activation in Alzheimer's disease (AD); however, their effects on amyloid pathology and neurodegeneration remain inconclusive. Here, we conditionally deleted one allele of myd88 gene specifically in microglia in APP/PS1-transgenic mice by 6 months and analyzed AD-associated pathologies by 9 months. We observed that heterozygous deletion of myd88 gene in microglia decreased cerebral amyloid β (Aβ) load and improved cognitive function of AD mice, which was correlated with reduced number of microglia in the brain and inhibited transcription of inflammatory genes, for example, tnf-α and il-1β, in both brain tissues and individual microglia. To investigate mechanisms underlying the pathological improvement, we observed that haploinsufficiency of MyD88 increased microglial recruitment toward Aβ deposits, which might facilitate Aβ clearance. Microglia with haploinsufficient expression of MyD88 also increased vasculature in the brain of APP/PS1-transgenic mice, which was associated with up-regulated transcription of osteopontin and insulin-like growth factor genes in microglia. Moreover, MyD88-haploinsufficient microglia elevated protein levels of LRP1 in cerebral capillaries of APP/PS1-transgenic mice. Cell culture experiments further showed that treatments with interleukin-1β decreased LRP1 expression in pericytes. In summary, haploinsufficiency of MyD88 in microglia at a late disease stage attenuates pro-inflammatory activation and amyloid pathology, prevents the impairment of microvasculature and perhaps also protects LRP1-mediated Aβ clearance in the brain of APP/PS1-transgenic mice, all of which improves neuronal function of AD mice.
DOI of the first publication: 10.1002/glia.24007
Link to this record: urn:nbn:de:bsz:291--ds-346100
ISSN: 1098-1136
Date of registration: 1-Sep-2021
Description of the related object: Supporting Information
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Chirurgie
M - Neurologie und Psychiatrie
M - Neuropathologie
Professorship: M - Prof. Dr. Klaus Faßbender
M - Prof. Dr. Michael D. Menger
M - Prof. Dr. Walter Schulz-Schaeffer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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