Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, 230001, People's Republic of China.
Department of Ultrasound, Hefei Hospital affiliated to Anhui Medical University: The Second People's Hospital of Hefei, Hefei, Anhui Province, 230011, People's Republic of China.
Mol Neurobiol. 2024 Sep;61(9):6984-6996. doi: 10.1007/s12035-024-03953-8. Epub 2024 Feb 16.
Rs3851179, a variant of PICALM gene, and age are the risk factors of Alzheimer's disease (AD). AD is divided into early-onset AD (EOAD, < 65 years) and late-onset AD (LOAD, ≥ 65 years) by age. The purpose was to investigate the impact of different genotypes of PICALM rs3851179 on brain atrophy and cognitive decline across the AD continuum in different age groups. Four hundred seven cognitive normal (CN) controls, 362 mild cognitive impairment (MCI) patients, and 94 AD patients were enrolled to assess the interaction between AD continuum, age status, and PICALM on gray matter volume (GMV), global cognition, memory function, and executive function using full factorial ANCOVA (3 × 2 × 2). The interaction between AD continuum and PICALM significantly affected the GMV of the left putamen (PUT.L). rs3851179 A-allele carriers did not show a significant decrease in PUT.L GMV from CN to MCI to AD, while GG-allele carriers did. The interaction between AD continuum and age status was significant on GMV of the left angular gyrus (ANG.L) and right superior occipital gyrus (SOG.R). LOAD had higher GMV of ANG.L and SOG.R than EOAD. The interactive effects among AD continuum, age status, and PICALM were not significant on GMV but were significant on global cognition and executive function. The A-allele was found to have a protective effect on global cognition and executive function in EOAD, but not significantly so in LOAD. PICALM rs3851179 A-allele might alleviate the atrophy of PUT.L across the AD continuum than GG-allele. Age status did not affect the interaction between AD continuum and PICALM on brain atrophy. The ANG.L and SOG.R atrophied more severely in EOAD than in LOAD. Rs3851179 A-allele was protective for global cognition and executive function in EOAD.
rs3851179 是 PICALM 基因的一种变体，年龄是阿尔茨海默病（AD）的危险因素。AD 按发病年龄分为早发性 AD（EOAD，<65 岁）和晚发性 AD（LOAD，≥65 岁）。本研究旨在探讨不同 PICALM rs3851179 基因型在不同年龄组 AD 连续体中对脑萎缩和认知衰退的影响。共纳入 407 例认知正常（CN）对照者、362 例轻度认知障碍（MCI）患者和 94 例 AD 患者，采用完全因子方差分析（3×2×2）评估 AD 连续体、年龄状态和 PICALM 对灰质体积（GMV）、总体认知、记忆功能和执行功能的交互作用。AD 连续体与 PICALM 的相互作用显著影响左侧壳核（PUT.L）的 GMV。rs3851179 A 等位基因携带者从 CN 到 MCI 再到 AD，PUT.L GMV 没有明显下降，而 GG 等位基因携带者则有明显下降。AD 连续体与年龄状态的相互作用对左侧角回（ANG.L）和右侧顶枕叶（SOG.R）的 GMV 有显著影响。LOAD 的 ANG.L 和 SOG.R GMV 高于 EOAD。AD 连续体、年龄状态和 PICALM 之间的交互作用在 GMV 上不显著，但在总体认知和执行功能上显著。在 EOAD 中，A 等位基因对总体认知和执行功能有保护作用，但在 LOAD 中则不显著。与 GG 等位基因相比，PICALM rs3851179 A 等位基因可能减轻 AD 连续体中 PUT.L 的萎缩。年龄状态不影响 AD 连续体与 PICALM 之间脑萎缩的相互作用。EOAD 中 ANG.L 和 SOG.R 的萎缩比 LOAD 更严重。在 EOAD 中，rs3851179 A 等位基因对总体认知和执行功能有保护作用。
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