Public Health

Dr. Hannah Stocker (MPH)
Netzwork Aging Research
Bergheimer Straße 20
D-69115 Heidelberg

Phone: +49 (0)6221 54 8120
stocker(at)nar.uni-heidelberg.de
Fellows: Prof. Dr. Hermann Brenner

The role of genetic risk scores in the detection and prevention of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disease affecting 1 in 10 older adults aged 65 years and older. The heritability of late-onset AD has been estimated at 74%. The ε4 allele of the gene encoding the Apolipoprotein E, is a strong genetic risk factor of late onset AD. However, only 40-65% of people with AD are ε4 carriers insinuating additional associated genetic loci. In recent years large-scale genome-wide association studies have identified at least 21 additional genetic loci associated with AD, considerably advancing the development of genetic risk scores (GRSs) for AD. GRSs are used to determine the genetic risk for a disease through the collective consideration of many individual small effects of genetic loci which together could account for substantial differences in risk. GRSs for AD utilize AD associated single nucleotide polymorphisms (SNPs) and corresponding associations to form a composite risk score encompassing individual risk of each genetic loci. By identifying people at risk of AD before clinical manifestation, GRSs have the potential to contribute to an accurate and individualized prediction of AD risk. The overall aim of this dissertation is to construct and validate a genetic risk score for AD in a large German cohort study and to investigate the common genetic architecture between AD and associated comorbidities. The data for this project is based on the ESTHER cohort study (http://esther.dkfz.org/esther/).

Publications

2024

• Angelidou, I. A., Stocker, H., Beyreuther, K., & Teichmann, B. (2024). Validation of the “Perceptions Regarding pRE-Symptomatic Alzheimer’s Disease Screening” (PRE-ADS) Questionnaire in the German Population: Attitudes, Motivations, and Barriers to Pre-Symptomatic Dementia Screening. Journal of Alzheimer's Disease, 97(1), 309–325. https://doi.org/10.3233/JAD-230961

2023

• Huemer, M.-T., Kluttig, A., ... Stocker, H., … Thorand, B. (2023). Grip strength values and cut-off points based on over 200,000 adults of the German National Cohort - a comparison to the EWGSOP2 cut-off points. Age and Ageing, 52(1). https://doi.org/10.1093/ageing/afac324
• Perna, L., Mons, U., Stocker, H., Beyer, L., Beyreuther, K., Trares, K., Holleczek, B., Schöttker, B., Perneczky, R., Gerwert, K., & Brenner, H. High cholesterol levels change the association of biomarkers of neurodegenerative diseases with dementia risk: Findings from a population-based cohort. Alzheimer's & Dementia, n/a(n/a). https://doi.org/https://doi.org/10.1002/alz.12933
• Stocker, H., Beyer, L., Trares, K., Perna, L., Rujescu, D., Holleczek, B., Beyreuther, K., Gerwert, K., Schöttker, B., & Brenner, H. (2023). Association of Kidney Function With Development of Alzheimer Disease and Other Dementias and Dementia-Related Blood Biomarkers. JAMA Network Open, 6(1), e2252387. https://doi.org/10.1001/jamanetworkopen.2022.52387.

2022

• Giaccherini, M., Farinella, R., ... Stocker, H., ... Campa, D. (2022). Association between a polymorphic variant in the CDKN2B-AS1/ANRIL gene and pancreatic cancer risk. International journal of cancer, 10.1002/ijc.34383. Advance online publication. https://doi.org/10.1002/ijc.34383
• Stocker, H., Beyer, L., Perna, L., Rujescu, D., Holleczek, B., Beyreuther, K., Stockmann, J., Schöttker, B., Gerwert, K., & Brenner, H. (2022). Association of plasma biomarkers, p-tau181, glial fibrillary acidic protein, and neurofilament light, with intermediate and long-term clinical Alzheimer's disease risk: Results from a prospective cohort followed over 17 years. Alzheimer's & dementia : the journal of the Alzheimer's Association, 19(1), 25–35. https://doi.org/10.1002/alz.12614
• Lam, S. Y., Mommersteeg, M. C., ... Stocker, H., Brenner, H., Levy, D., Hwang, S. J., Wood, A. C., Rich, S. S., Rotter, J. I., Taylor, K. D., Tracy, R. P., … Peppelenbosch, M. P. (2022). Toll-Like Receptor 1 Locus Re-examined in a Genome-Wide Association Study Update on Anti-Helicobacter pylori IgG Titers. Gastroenterology, 162(6), 1705–1715. https://doi.org/10.1053/j.gastro.2022.01.011
• Peduzzi, G., Archibugi, L., ... Brenner, H., Vermeulen, R. C. H., Talar-Wojnarowska, R., Vanella, G., Tavano, F., Lucchesi, M., Mohelnikova-Duchonova, B., Chen, X., Kiudelis, V., Hegyi, P., Oliverius, M., Stocker, H., … Campa, D. (2022). Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women. Scientific reports, 12(1), 18100. https://doi.org/10.1038/s41598-022-22973-9
• Trares, K., Bhardwaj, M., Perna, L., Stocker, H., Petrera, A., Hauck, S. M., Beyreuther, K., Brenner, H., & Schöttker, B. (2022). Association of the inflammation-related proteome with dementia development at older age: results from a large, prospective, population-based cohort study. Alzheimer's research & therapy, 14(1), 128. https://doi.org/10.1186/s13195-022-01063-y
• Beyer, L.*, Stocker, H*., Rujescu, D., Holleczek, B., Stockmann, J., Nabers, A., Brenner, H., & Gerwert, K. (2022). Amyloid-beta misfolding and GFAP predict risk of clinical Alzheimer's disease diagnosis within 17 years. Alzheimer's & dementia : the journal of the Alzheimer's Association, 10.1002/alz.12745. Advance online publication. https://doi.org/10.1002/alz.12745. *Shared first authorship
• Gorski, M., Rasheed, H., Teumer, A., ... Stocker, H.,... Heid, I. M. (2022). Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies. Kidney international, 102(3), 624–639. https://doi.org/10.1016/j.kint.2022.05.021
• Möllers, T., Stocker, H., Perna, L., Rujescu, D., Holleczek, B., Schöttker, B., & Brenner, H. (2022). Subjective short-term memory difficulties at ages 50-75 predict dementia risk in a community-based cohort followed over 17 years. Age and ageing, 51(6), afac113. https://doi.org/10.1093/ageing/afac113
• Nguyen, T. N. M., Chen, L. J., Trares, K., Stocker, H., Holleczek, B., Beyreuther, K., Brenner, H., & Schöttker, B. (2022). Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer's disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies. Alzheimer's research & therapy, 14(1), 75. https://doi.org/10.1186/s13195-022-01017-4
• Lam, S. Y., Mommersteeg, M. C., ... Stocker, H., Brenner, H., Levy, D., Hwang, S. J., Wood, A. C., Rich, S. S., Rotter, J. I., Taylor, K. D., Tracy, R. P., … Peppelenbosch, M. P. (2022). Toll-Like Receptor 1 Locus Re-examined in a Genome-Wide Association Study Update on Anti-Helicobacter pylori IgG Titers. Gastroenterology, 162(6), 1705–1715. https://doi.org/10.1053/j.gastro.2022.01.011
• Gentiluomo, M., Giaccherini, M., Gào, X., Guo, F., Stocker, H., Schöttker, B., Brenner, H., Canzian, F., & Campa, D. (2022). Genome-wide association study of mitochondrial copy number. Human molecular genetics, 31(8), 1346–1355. https://doi.org/10.1093/hmg/ddab341
• Perna, L., Trares, K., Perneczky, R., Tato, M., Stocker, H., Möllers, T., Holleczek, B., Schöttker, B., & Brenner, H. (2022). Risk of Late-Onset Depression and Cognitive Decline: Results From Inflammatory Proteome Analyses in a Prospective Population-Based Cohort Study. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 30(6), 689–700. https://doi.org/10.1016/j.jagp.2021.12.001
• Erhardt, A., Gelbrich, G., Klinger-König, J., Streit, F., Kleineidam, L., Riedel-Heller, S. G., NAKO Investigators (Stocker, H.), Schmidt, B., Schmiedek, F., Wagner, M., Grabe, H. J., Rietschel, M., Berger, K., & Deckert, J. (2022). Generalised anxiety and panic symptoms in the German National Cohort (NAKO). The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 1–16. Advance online publication. https://doi.org/10.1080/15622975.2021.2011409

2021

• Schlosser, P., Tin, A., ... M., Brenner, H., Breteler, M. M. B., Carmeli, C., ... Stocker, H., … Teumer, A. (2021). Meta-analyses identify DNA methylation associated with kidney function and damage. Nature communications, 12(1), 7174. https://doi.org/10.1038/s41467-021-27234-3
• Tin, A., Schlosser, P., Matias-Garcia, P. R., ... Stocker, H., … Köttgen, A. (2021). Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus. Nature communications, 12(1), 7173. https://doi.org/10.1038/s41467-021-27198-4
• Möllers, T., Stocker, H., Perna, L., Nabers, A., Rujescu, D., Hartmann, A. M., Holleczek, B., Schöttker, B., Gerwert, K., & Brenner, H. (2021). Aβ misfolding in blood plasma is inversely associated with body mass index even in middle adulthood. Alzheimer's research & therapy, 13(1), 145. https://doi.org/10.1186/s13195-021-00889-2
• Stocker, H., Nabers, A., Perna, L., Möllers, T., Rujescu, D., Hartmann, A. M., Holleczek, B., Schöttker, B., Stockmann, J., Gerwert, K., & Brenner, H. (2021). Genetic predisposition, Aβ misfolding in blood plasma, and Alzheimer's disease. Translational psychiatry, 11(1), 261. https://doi.org/10.1038/s41398-021-01380-0
• Möllers, T., Stocker, H., Perna, L., Nabers, A., Rujescu, D., Hartmann, A. M., Holleczek, B., Schöttker, B., Gerwert, K., & Brenner, H. (2021). Aβ misfolding in blood plasma measured by immuno-infrared-sensor as an age-independent risk marker of Alzheimer's disease. Alzheimer's & dementia (Amsterdam, Netherlands), 13(1), e12151. https://doi.org/10.1002/dad2.12151

2020

• Stocker, H., Perna, L., Weigl, K., Möllers, T., Schöttker, B., Thomsen, H., ... & Brenner, H. (2020). Prediction of clinical diagnosis of Alzheimer’s disease, vascular, mixed, and all-cause dementia by a polygenic risk score and APOE status in a community-based cohort prospectively followed over 17 years. Molecular psychiatry, 1-11.
• Trares, K., Gào, X., Perna, L., Rujescu, D., Stocker, H., Möllers, T., ... & Schöttker, B. (2020). Associations of urinary 8‐iso‐prostaglandin F2α levels with all‐cause dementia, Alzheimer's disease, and vascular dementia incidence: results from a prospective cohort study. Alzheimer's & Dementia, 16(5), 804-813.
• Möllers, T., Perna, L., Stocker, H., Ihle, P., Schubert, I., Schöttker, B., ... & Brenner, H. (2020). New use of psychotropic medication after hospitalization among people with dementia. International journal of geriatric psychiatry, 35(6), 640-649.

2019

• Möllers, T., Stocker, H., Wei, W., Perna, L., & Brenner, H. (2019). Length of hospital stay and dementia: a systematic review of observational studies. International journal of geriatric psychiatry, 34(1), 8-21.
• Stocker, H., Nabers, A., Perna, L., Möllers, T., Rujescu, D., Hartmann, A., ... & Brenner, H. (2019). Prediction of Alzheimer's disease diagnosis within 14 years through Aβ misfolding in blood plasma compared to APOE4 status, and other risk factors. Alzheimer's & Dementia.

Vita

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