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  • 1
    Online Resource
    Online Resource
    Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population
    Springer Science and Business Media LLC ; 2021
    In:  Alzheimer's Research & Therapy Vol. 13, No. 1 ( 2021-12)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer’s disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population. Methods One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI] , and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. Results In addition to APOE , we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity ( p 〈  0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level ( p 〈  5.0 × 10 −8 ). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74–0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. Conclusion The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-021-00854-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2506521-X
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  • 2
    Online Resource
    Online Resource
    Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes
    American Medical Association (AMA) ; 2022
    In:  JAMA Network Open Vol. 5, No. 12 ( 2022-12-15), p. e2247162-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 12 ( 2022-12-15), p. e2247162-
    Abstract: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. Objective To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. Design, Setting, and Participants This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Main Outcomes and Measures Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid β deposition (Aβ). Results A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P   & amp;lt; .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aβ deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. Conclusions and Relevance In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2022.47162
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2931249-8
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  • 3
    Online Resource
    Online Resource
    Cognitive trajectories of patients with focal ß-amyloid deposition
    Springer Science and Business Media LLC ; 2021
    In:  Alzheimer's Research & Therapy Vol. 13, No. 1 ( 2021-12)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition. Methods We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI] , and 50 Alzheimer’s disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18 F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group. Results Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7–9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1–3 or 4–6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex. Conclusions When predicting cognitive decline of patients with focal Aß deposition, the patients’ cognitive level, extent, and location of the focal involvement are important.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-021-00787-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    Visual Rating of Posterior Atrophy as a Marker of Progression to Dementia in Mild Cognitive Impairment Patients
    IOS Press ; 2016
    In:  Journal of Alzheimer's Disease Vol. 55, No. 1 ( 2016-11-01), p. 137-146
    Details
    In: Journal of Alzheimer's Disease, IOS Press, Vol. 55, No. 1 ( 2016-11-01), p. 137-146
    Type of Medium: Online Resource
    ISSN: 1387-2877 , 1875-8908
    URL: Article
    DOI: 10.3233/JAD-160339
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2016
    detail.hit.zdb_id: 2070772-1
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  • 5
    Online Resource
    Online Resource
    Posterior atrophy predicts time to dementia in patients with amyloid-positive mild cognitive impairment
    Springer Science and Business Media LLC ; 2017
    In:  Alzheimer's Research & Therapy Vol. 9, No. 1 ( 2017-12)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2017-12)
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-017-0326-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2506521-X
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