OBJECTIVE: Genome-wide association studies have linked variants in @entity16014 ( @entity16014 ) and @entity68734 with @entity195 ( @entity195 ) and @entity195 endophenotypes. Here, we pursue a targeted analysis of the TREM locus in relation to @entity73 and pathological features of @entity195 . METHODS: Clinical, cognitive, and neuropathological phenotypes were collected in 3 prospective cohorts on aging (n   =   3,421 subjects). Our primary analysis was an association with @entity527 pathology. To functionally characterize the associated variants, we used flow cytometry to measure @entity15054 expression on monocytes. RESULTS: We provide evidence that an intronic variant, @entity68735 (G) , in @entity15054 , is associated with an increased burden of @entity527 (p   =   3.7 * 10(-4) ), diffuse plaques (p   =   4.1 * 10(-3) ), and Ab density (p   =   2.6 * 10(-3) ) as well as an increased rate of @entity73 (p   =   5.3 * 10(-3) ). A variant upstream of @entity16014 , @entity68736 (C) , is independently associated with an increased tau tangle density (p   =   4.9 * 10(-4) ), an increased burden of @entity3072 (p   =   9.1 * 10(-3) ), and an increased rate of @entity73 (p   =   2.3 * 10(-3) ). Finally, a cytometric analysis shows that the @entity15054 @entity68735 (G) allele is associated with decreased @entity15054 expression on the surface of myeloid cells (p   =   1.7 * 10(-3) ). INTERPRETATION: We provide evidence that 2 common variants within the TREM locus are associated with pathological features of @entity195 and aging-related @entity73 . Our evidence suggests that these variants are likely to be independent of known @entity195 variants and that they may work through an alteration of myeloid cell function.

A XXXX variant alters the accumulation of Alzheimer-related amyloid pathology.

@entity15054 :: ('54210', 'Gene') :: ['TREM1'] @entity527 :: ('MESH:D058225', 'Disease') :: ['neuritic plaque', 'neuritic plaques'] @entity16014 :: ('54209', 'Gene') :: ['TREM2', 'triggering receptor expressed on myeloid cells 2'] @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive decline'] @entity3072 :: ('MESH:C536599', 'Disease') :: ['neurofibrillary tangles'] @entity68734 :: ('79865', 'Gene') :: ['TREML2'] @entity68736 :: ('rs7759295', 'SNP') :: ['rs7759295'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', 'Alzheimer disease'] @entity68735 :: ('rs6910730', 'SNP') :: ['rs6910730']
@entity15054 :: (54210,Gene) :: ['TREM1']
