Abstract:

A lower body mass is associated with the progression of Alzheimer's disease (AD) and the risk of mortality in patients with AD; however, evidence of genetic determinants of decreased body mass in cognitively impaired older adults is limited. We therefore investigated the genetic effect of APOE-ε4 on body composition in older adults with mild cognitive impairment (MCI) and early-to-moderate-stage AD. A total of 1631 outpatients (aged 65-89 years) with MCI and early-to-moderate-stage AD were evaluated for the association between body composition and APOE-ε4 status. After adjusting for covariates, including cognitive function evaluated with the Mini-Mental State Examination, the presence of the APOE-ε4 was associated with lower weight (β = -1.116 ± 0.468 kg per presence, p = 0.017), fat mass (β = -1.196 ± 0.401 kg per presence, p = 0.003), and percentage of body fat (β = -1.700 ± 0.539% per presence, p = 0.002) in women but not in men. Additionally, the impact of APOE-ε4 on measures of body composition in women was more remarkable in MCI than in AD patients. The presence of the APOE-ε4 allele was associated with lower fat mass, particularly in women with MCI, independent of cognitive decline.

日本語要旨:

孤発性アルツハイマー病（AD）患者の全ゲノムシークエンス解析から、日本人など東アジア人に特異的に見られるAD発症リスク変異をOR51G1遺伝子とMLKL遺伝子に見出しました。またAD関連遺伝子群の遺伝間相互作用ネットワーク解析から、4個の主要なハブ遺伝子（NCOR2、DMD、NEDD4、PLEC）を同定しました。これらの知見は、アミロイド仮説だけでは説明がつかないADの複雑な発症メカニズムの解明と新たな治療法の開発に寄与するものと期待されます。