Neurotoxicity from innate immune response is greatest with targeted replacement of ε4 allele of apolipoprotein E gene and is mediated by microglial p38MAPK
- 2 February 2006
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 20 (6) , 797-799
- https://doi.org/10.1096/fj.05-5423fje
Abstract
SPECIFIC AIMSGlial innate immune response has been associated with several degenerative diseases of brain including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), traumatic brain injury, and HIV-encephalitis; and numerous genetic studies have associated inheritance of APOE4 with increased risk, earlier onset, or poorer clinical outcome for these same diseases of brain. ApoE has an immune modulatory function, at least in the peripheral adaptive immune response to some bacteria and viruses. Here we tested the hypothesis that inheritance of different APOE alleles significantly modulates neurotoxicity arising from CD14/Toll-like receptor (TLR) 4-activated glial innate immune response by lipopolysaccharide (LPS).PRINCIPAL FINDINGS1. Neurotoxicity from glial innate immune response is greatest with TR APOE4 microglia in primary dissociated culturesWe exposed primary dissociated cultures of wild-type (WT) neurons mixed with or without TR APOE microglia or astrocytes to LP...Keywords
Funding Information
- Nancy and Buster Alvord Endowment
- National Institutes of Health (AG-24011, AG-05136)
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