Ethnic differences in the frequency of β-amyloid deposition in cognitively normal individuals

Abstract

We investigated which factors might explain the differences between the frequencies of brain β-amyloid (Aβ) deposition in Korean and European cognitively normal individuals (CNs). We recruited 434 Korean CNs from the Samsung Medical Center (SMC) and 323 European CNs from the US Alzheimer's Disease Neuroimaging Initiative (ADNI). The Korean CNs showed lower education duration (11.8 ± 4.8 years vs. 16.8 ± 2.5 years, p < 0.001) than the European CNs. The frequency of Aβ (+) was higher in the European CNs (32.8%) than in the Korean CNs (20.0%; p < 0.001). In the SMC genome-wide association study (GWAS), 10 variants (including rs7481773 on chromosome 11, located near the brain-derived neurotrophic factor gene) exceeded the genome-wide significance level (p < 5 × 10⁻⁸). Especially, rs7481773 carriers showed more rapid decline in memory function than non–carriers (p = 0.048). However, this association was not observed in the ADNI GWAS. Our findings suggested that the different frequencies of Aβ (+) between CN Koreans and Europeans might be related to decreased cognitive reserve or genetic factors.

Introduction

Cerebral β-amyloid (Aβ) deposition is the earliest recognizable pathologic change in Alzheimer's disease (AD) (Bateman et al., 2012). In particular, the prevalence estimates of Aβ pathology and their related factors in cognitively normal (CN) individuals are required to understand the disease progression of AD and to design AD studies (Jansen et al., 2015).

The risk of AD dementia is substantially driven by cultural and genetic factors (Kunkle et al., 2019). Several factors related to cognitive reserve, including education (Stern et al., 2020) and socioeconomic status in childhood, may affect the development of dementia. The apolipoprotein E (APOE) ε4 allele is an important risk factor for the development of AD dementia. A recent genome-wide association study (GWAS) reported over 20 genetic loci that were associated with the development of AD (Jansen et al., 2019). Furthermore, specific genetic variants have exhibited different associations with AD in Europeans drawn from the US and other countries and Asians drawn from several countries in Asia (Han et al., 2018; Han et al., 2019). Thus, it would be reasonable to expect genetic variants to exhibit associations with Aβ in specific populations, resulting differences in Aβ positivity among ethnic groups. In fact, differences have been observed in the frequency of amyloid positivity in CN across different populations despite including a relatively small number of non–European participants, including Asian individuals (Sperling et al., 2020).

In the present study, we compared the frequency of Aβ (+) in CN populations between a Korean, and a European cohort based on the Alzheimer's Disease Neuroimaging Initiative (ADNI). We investigated which factors, including age, sex, education level, and genetics, contributed to the difference in the frequency of Aβ (+) in CN populations between these 2 ethnically different cohorts.