The triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial innate immune receptor associated with a lethal form of early, progressive dementia, Nasu-Hakola disease, and with an increased risk of Alzheimer's disease.
Recent studies have found an association between functional variants in TREM2 and PLD3 and Alzheimer's disease (AD), but their effect on cognitive function is unknown.
Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson's disease.
Meta-analysis of the 2 family-based and the 5 case-control cohorts yielded a p value of 0.0029, while the overall summary estimate (using case-control data only) resulted in an odds ratio of 1.67 (95% confidence interval 0.95-2.92) for the association between the TREM2R47H and increased AD risk.
These data suggest that the AD-associated TREM2R47H variant increases risk for AD by conferring a loss of TREM2 function and enhancing neuritic dystrophy around plaques.
Variants of triggering receptor expressed on myeloid cells 2 (TREM2) are associated with an increased incidence of Alzheimer's disease, as well as other neurodegenerative disorders.
Our study suggests that Vps35/retromer is responsible for recycling of Trem2 in the regulation of microglial function such as proinflammatory responses, whereas R47H mutation impairs Trem2 trafficking, which might contribute to AD.
We measured soluble TREM2 (sTREM2) in the CSF of a large AD case-control dataset (n = 180) and 40 TREM2 risk variant carriers to determine whether CSF sTREM2 levels are associated with AD status or mutation status.
<b>Background:</b> rs9357347 located at the triggering receptor expressed on myeloid cells (<i>TREM</i>) gene cluster could increase TREM2 and TREM-like transcript 1 (TREML1) brain gene expression, which is considered to play a protective role against Alzheimer's disease (AD).
Genome-wide association studies have linked variants in TREM2 (triggering receptor expressed on myeloid cells 2) and TREML2 with Alzheimer disease (AD) and AD endophenotypes.
Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.
Independent voxel-based morphometry analysis of the Spanish set as well as conjunction and joint analyses revealed substantial gray matter loss in orbitofrontal cortex and anterior cingulate cortex with relative preservation of parietal lobes in AD and/or mild cognitive impairment TREM2p.R47H carriers, suggesting that TREM2p.R47H variant is associated with certain clinical and neuroimaging AD features in addition to the increased TREM2p.R47H atrophy in temporal lobes as described previously.
Mutations and/or differential expression of microglial receptors such as TREM2, CD33, and CR3 have been strongly associated with an increased risk of developing AD.
(2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques.
Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease.