Journal article
The effect of amyloid on microglia-neuron interactions before plaque onset occurs independently of TREM2 in a mouse model of Alzheimer's disease
Neurobiology of disease, Vol.145, pp.105072-105072
11/01/2020
DOI: 10.1016/j.nbd.2020.105072
PMCID: PMC7808254
PMID: 32890775
Abstract
Genetic studies identified mutations in several immune-related genes that confer increased risk for developing Alzheimer's disease (AD), suggesting a key role for microglia in AD pathology. Microglia are recruited to and actively modulate the local toxicity of amyloid plaques in models of AD through these cells' transcriptional and functional reprogramming to a disease-associated phenotype. However, it remains unknown whether microglia actively respond to amyloid accumulation before plaque deposition in AD. We compared microglial interactions with neurons that exhibit amyloid accumulation to those that do not in 1-month-old 5XFAD mice to determine which aspects of microglial morphology and function are altered by early 6E10 + amyloid accumulation. We provide evidence of preferential microglial process engagement of amyloid laden neurons. Microglia, on exposure to amyloid, also increase their internalization of neurites even before plaque onset. Unexpectedly, we found that triggering receptor expressed on myeloid cells 2 (TREM2), which is critical for microglial responses to amyloid plaque pathology later in disease, is not required for enhanced microglial interactions with neurons or neurite internalization early in disease. However, TREM2 was still required for early morphological changes exhibited by microglia. These data demonstrate that microglia sense and respond to amyloid accumulation before plaques form using a distinct mechanism from the TREM2-dependent pathway required later in disease.
Details
- Title: Subtitle
- The effect of amyloid on microglia-neuron interactions before plaque onset occurs independently of TREM2 in a mouse model of Alzheimer's disease
- Creators
- Victoria E. von Saucken - Indiana University – Purdue University IndianapolisTaylor R. Jay - Case Western Reserve UniversityGary E. Landreth - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- Neurobiology of disease, Vol.145, pp.105072-105072
- DOI
- 10.1016/j.nbd.2020.105072
- PMID
- 32890775
- PMCID
- PMC7808254
- NLM abbreviation
- Neurobiol Dis
- ISSN
- 0969-9961
- eISSN
- 1095-953X
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- AG048704 / NIA National Research Service Award F31 AG051495; AG050597 / National Institute of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA BFG-15-364590 / Alzheimer's Association
- Language
- English
- Date published
- 11/01/2020
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9985112882102771
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