Gwangju Alzheimer's & Related Dementia Cohort Research Center, Chosun University, Gwangju, Republic of Korea.
Department of Biomedical Science, Chosun University, Gwangju, Republic of Korea.
PLoS One. 2022 Jul 13;17(7):e0270795. doi: 10.1371/journal.pone.0270795. eCollection 2022.
Hippocampal subfield atrophy is a prime structural change in the brain, associated with cognitive aging and neurodegenerative diseases such as Alzheimer's disease. Recent developments in genome-wide association studies (GWAS) have identified genetic loci that characterize the risk of hippocampal volume loss based on the processes of normal and abnormal aging. Polygenic risk scores are the genetic proxies mimicking the genetic role of the pre-existing vulnerabilities of the underlying mechanisms influencing these changes. Discriminating the genetic predispositions of hippocampal subfield atrophy between cognitive aging and neurodegenerative diseases will be helpful in understanding the disease etiology. In this study, we evaluated the polygenic risk of Alzheimer's disease (AD PGRS) for hippocampal subfield atrophy in 1,086 individuals (319 cognitively normal (CN), 591 mild cognitively impaired (MCI), and 176 Alzheimer's disease dementia (ADD)). Our results showed a stronger association of AD PGRS effect on the left hemisphere than on the right hemisphere for all the hippocampal subfield volumes in a mixed clinical population (CN+MCI+ADD). The subfields CA1, CA4, hippocampal tail, subiculum, presubiculum, molecular layer, GC-ML-DG, and HATA showed stronger AD PGRS associations with the MCI+ADD group than with the CN group. The subfields CA3, parasubiculum, and fimbria showed moderately higher AD PGRS associations with the MCI+ADD group than with the CN group. Our findings suggest that the eight subfield regions, which were strongly associated with AD PGRS are likely involved in the early stage ADD and a specific focus on the left hemisphere could enhance the early prediction of ADD.
海马亚区萎缩是大脑的主要结构变化之一，与认知老化和神经退行性疾病如阿尔茨海默病有关。全基因组关联研究（GWAS）的最新进展已经确定了遗传位点，这些遗传位点基于正常和异常衰老的过程，描述了海马体积损失的风险。多基因风险评分是遗传代理，模拟了影响这些变化的潜在机制的预先存在的脆弱性的遗传作用。区分认知老化和神经退行性疾病中海马亚区萎缩的遗传倾向有助于理解疾病的病因。在这项研究中，我们评估了阿尔茨海默病（AD）的多基因风险评分（AD PGRS）对 1086 个人（319 名认知正常（CN）、591 名轻度认知障碍（MCI）和 176 名阿尔茨海默病痴呆（ADD））的海马亚区萎缩的影响。我们的结果表明，在混合临床人群（CN+MCI+ADD）中，AD PGRS 对左侧海马亚区的影响比对右侧更强。在 MCI+ADD 组中，CA1、CA4、海马尾部、下托、前下托、分子层、GC-ML-DG 和 HATA 等亚区与 AD PGRS 的相关性更强，而在 CN 组中则较弱。在 MCI+ADD 组中，CA3、副下托和纤维弓与 AD PGRS 的相关性略高。我们的研究结果表明，与 AD PGRS 强烈相关的八个亚区可能与早期的 ADD 有关，并且特别关注左侧可能会增强对 ADD 的早期预测。
