Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.

特定大脑区域的神经元进行性丧失是阿尔茨海默病（AD）的表现之一。人们投入了大量精力来研究脑萎缩和AD。然而，皮质结构与AD之间的因果关系尚不清楚。我们进行了双向双样本孟德尔随机化分析，以研究皮质结构（整个皮质和 34 个皮质区域的表面积和厚度）与 AD 风险之间的因果关系。用作工具的遗传变异来自对皮质结构（33,992 名欧洲血统参与者）和 AD（AD 和代理 AD，71,880 例病例，383,378 名对照）的大型全基因组关联荟萃分析。我们发现颞极表面积减少（OR（95% CI）：0.95（0.9，0.997）， p = 0.04）和楔骨厚度减少（OR（95% CI）：0.93（0.89，p = 0.04）之间存在暗示性关联。 0.98), p = 0.006) AD 风险较高。我们还发现 AD 脆弱性与中央前 ( β (SE): –43.4 (21.3), p = 0.042) 和扣带峡部 ( β (SE): –18.5 (7.3), p = 0.011）。然而，皮质结构与 AD 之间因果关系的 Bonferroni 校正p值均未达到阈值。我们提供了暗示性证据，证明颞极和楔骨萎缩与 AD 风险较高之间存在关联。另一方面，AD 易感性与中央前区和扣带峡部表面积减少之间存在暗示性因果关系。我们的研究结果揭示了皮质结构与 AD 发生的关联。