Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas, USA.
Boston University School of Medicine, Department of Neurology, Boston, Massachusetts, USA.
Alzheimers Dement. 2023 Aug;19(8):3496-3505. doi: 10.1002/alz.12954. Epub 2023 Feb 22.
We investigated associations of obesity with the expression of Alzheimer's disease (AD)-related genes in a large community-based cohort.
The sample consisted of 5619 participants from the Framingham Heart Study. Obesity metrics included body mass index (BMI) and waist-to-hip ratio (WHR). Gene expression was measured for a set of 74 AD-related genes, derived by integrating genome-wide association study results with functional genomics data.
Obesity metrics were associated with the expression of 21 AD-related genes. The strongest associations were observed with CLU, CD2AP, KLC3, and FCER1G. Unique associations were noted with TSPAN14, SLC24A4 for BMI, and ZSCAN21, BCKDK for WHR. After adjustment for cardiovascular risk factors, 13 associations remained significant for BMI and 8 for WHR. Dichotomous obesity metrics exhibited unique associations with EPHX2 for BMI, and with TSPAN14 for WHR.
Obesity was associated with AD-related gene expression; these findings shed light on the molecular pathways linking obesity to AD.
我们在一个大型的基于社区的队列中研究了肥胖与阿尔茨海默病(AD)相关基因表达之间的关联。
该样本由弗雷明汉心脏研究中的 5619 名参与者组成。肥胖指标包括体重指数(BMI)和腰臀比(WHR)。通过整合全基因组关联研究结果和功能基因组学数据,为一组 74 个 AD 相关基因的表达进行了测量。
肥胖指标与 21 个 AD 相关基因的表达有关。与 CLU、CD2AP、KLC3 和 FCER1G 观察到最强的关联。BMI 与 TSPAN14、SLC24A4,WHR 与 ZSCAN21、BCKDK 之间存在独特的关联。在调整心血管危险因素后,BMI 与 13 个关联仍然显著,WHR 与 8 个关联仍然显著。二分肥胖指标与 BMI 中的 EPHX2 和 WHR 中的 TSPAN14 存在独特的关联。
肥胖与 AD 相关基因的表达有关;这些发现为肥胖与 AD 之间的分子途径提供了线索。