Breddels Esmee M, Snihirova Yelyzaveta, Pishva Ehsan, Gülöksüz Sinan, Blokland Gabriëlla Am, Luykx Jurjen, Andreassen Ole A, Linden David Ej, van der Meer Dennis
Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Faculty of Health and Life Sciences, Medical School, University of Exeter, Exeter, UK.
J Alzheimers Dis Rep. 2025 Mar 24;9:25424823251328300. doi: 10.1177/25424823251328300. eCollection 2025 Jan-Dec.
Late-onset Alzheimer's disease (LOAD) has been associated with alterations in the morphology of multiple brain structures, and it is likely that disease mechanisms differ between brain regions. Coupling genetic determinants of LOAD with measures of brain morphology could localize and identify primary causal neurobiological pathways.
To determine causal pathways from genetic risk variants of LOAD via brain morphology to LOAD.
Mediation and Mendelian randomization (MR) analysis were performed using common genetic variation, T1 MRI and clinical data collected by UK Biobank and Alzheimer's Disease Neuroimaging Initiative.
Thickness of the entorhinal cortex and the volumes of the hippocampus, amygdala and inferior lateral ventricle mediated the effect of ε4 on LOAD. MR showed that a thinner entorhinal cortex, a smaller hippocampus and amygdala, and a larger volume of the inferior lateral ventricles, increased the risk of LOAD as well as vice versa.
Combining neuroimaging and genetic data can give insight into the causal neuropathological pathways of LOAD.
晚发型阿尔茨海默病（LOAD）与多个脑结构的形态改变有关，且疾病机制在不同脑区可能存在差异。将LOAD的遗传决定因素与脑形态测量相结合，可定位并确定主要的因果神经生物学途径。
确定从LOAD的遗传风险变异通过脑形态到LOAD的因果途径。
使用英国生物银行和阿尔茨海默病神经影像倡议收集的常见遗传变异、T1加权磁共振成像（MRI）和临床数据进行中介分析和孟德尔随机化（MR）分析。
内嗅皮质厚度以及海马体、杏仁核和下侧脑室体积介导了ε4对LOAD的影响。MR显示，较薄的内嗅皮质、较小的海马体和杏仁核以及较大体积的下侧脑室会增加LOAD的风险，反之亦然。
结合神经影像学和遗传数据能够深入了解LOAD的因果神经病理途径。
