Publications
Text queries can be conducted by Author, Title, or Keyword.
GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP
Source: BRAIN A Journal of Neurology 2015 Oct;138:3076-3088.
Author: Ramanan VK, Risacher SL, Nho K, Kim S, Shen L, McDonald BC, Yoder KK, Hutchins GD, West JD, Tallman EF, Gao S, Foroud TM, Farlow MR, De Jager PL, Bennett DA, Aisen PS, Petersen RC, Jack CR Jr, Toga AW, Green RC, Jagust WJ, Weiner MW, Saykin AJ; Alzheimer’s Disease Neuroimaging Initiative (ADNI)
PubMed ID: 26268530
Abstract:
Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ?4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process.
Source: BRAIN A Journal of Neurology 2015 Oct;138:3076-3088.
Author: Ramanan VK, Risacher SL, Nho K, Kim S, Shen L, McDonald BC, Yoder KK, Hutchins GD, West JD, Tallman EF, Gao S, Foroud TM, Farlow MR, De Jager PL, Bennett DA, Aisen PS, Petersen RC, Jack CR Jr, Toga AW, Green RC, Jagust WJ, Weiner MW, Saykin AJ; Alzheimer’s Disease Neuroimaging Initiative (ADNI)
PubMed ID: 26268530
Abstract:
Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ?4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process.