Association between Alzheimer’s disease genes and trajectories of cognitive function decline in Han Chinese in Taiwan

Abstract

Genetic background has been considered one of the important contributors to the rate of cognitive decline among patients with Alzheimer’s disease (AD). We conducted a 4-year longitudinal follow-up study, recruited 255 AD and 44 mild cognitive impairment (MCI) patients, and used a data-driven trajectory analysis to examine the influence of selected AD risk genes on the age for and the rate of cognitive decline in Han Chinese population. Genotyping of selected single-nucleotide polymorphisms in the APOE , ABCA7 , SORL1 , BIN1 , GAB2 , and CD33 genes was conducted, and a Bayesian hierarchical model was fitted to analyze the trajectories of cognitive decline among different genotypes. After adjusting for sex and education years, the APOE ε4 allele was associated with an earlier mean change of −2.39 years in the age at midpoint of cognitive decline, the G allele in ABCA7 rs3764650 was associated with an earlier mean change of −1.75 years, and the T allele in SORL1 rs3737529 was associated with a later mean change of 2.6 years. Additionally, the rate of cognitive decline was associated with the APOE ε4 allele and SORL1 rs3737529. In summary, APOE and SORL1 might be the most important genetic factors related to cognitive decline in Han Chinese population.

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022

“…Normative data for many cortical and subcortical structures differed between ADNI and OASIS non‐Hispanic White participants and those in a second Korean cohort, affecting the performance of predictive algorithms 316 . Beyond the APOE ε4 allele, additional predictive associations were reported between alleles in ABCA7 and SORL1 and cognitive decline in a Han Chinese population from Taiwan compared to ADNI 317 …”

“… 316 Beyond the APOE ε4 allele, additional predictive associations were reported between alleles in ABCA7 and SORL1 and cognitive decline in a Han Chinese population from Taiwan compared to ADNI. 317 …”

“…316 Beyond the APOE ε4 allele, additional predictive associations were reported between alleles in ABCA7 and SORL1 and cognitive decline in a Han Chinese population from Taiwan compared to ADNI. 317 Differences in the prevalence of risk factors for AD have been identified among ethnocultural groups. Black/African-American ADNI participants had greater total and regional WMH burden compared to non-Hispanic White participants, largely attributable to the higher rate of vascular risk factors in Black/African-American groups.…”

Endophenotypic effects of the SORL1 variant rs2298813 on regional brain volume in patients with late-onset Alzheimer’s disease

“…Targeted single-nucleotide polymorphism (SNP) analyses and genome-wide association studies have validated the association not only in populations of Caucasian origin but also in Asian populations (Reitz et al, 2011;Lambert et al, 2013;Miyashita et al, 2013). A number of studies have shown significant associations between specific SORL1 polymorphisms and various phenotypes in AD patients, including lower Aβ levels in cerebrospinal fluid (Alexopoulos et al, 2011) and serum (Chou et al, 2016), increased tau protein in cerebrospinal fluid (Louwersheimer et al, 2015), hippocampal atrophy (Cuenco et al, 2008;Louwersheimer et al, 2015;Xiromerisiou et al, 2021), white matter hyperintensity (Cuenco et al, 2008), frontal symptoms (Huang et al, 2020), rate of cognitive decline (Hsieh et al, 2021), and Parkinsonian features (Cuccaro et al, 2016;Xiromerisiou et al, 2021).…”