Clinical characterization of two Flemish cohorts
The starting point for the PRISMA project, from which the various project worstreams were initiated, were two existing Flemish cohorts with both healthy people, as well as patients with Alzheimer's disease and a matching control for these patients. The profiling of these cohorts was the activity to kickstart PRISMA.
Deep-profiling of two Flemish cohorts
UZLeuven has followed two Flemish cohorts of individuals at different stages of AD and healthy control. These two cohorts have been followed and characterized over a longer period of time.
AD case-control cohort
The cohort with 179 AD cases and 98 spouse control which underwent six monthly clinical evluations including memory tests and neuropsychological assessments.
F-PACK cohort
The second cohort included 180 cognititvely healthy elderly volunteers for whom brain imaging (brain MRI and amyloid PET) is performed as well as blood sampling at different time points. All participants were cognitively normal at inclusion based on a conventional neuropsychological assessment. Inclusion was based on genetic stratification of the APOE Ɛ4 carrier status and GDNFval66met allele carrier status.
From these two cohorts biological material has been collected at different states for in depth characterization. For each AD case-control participant the genotype has been determined based on which a polygenic risk score has been calculated (see XXX). Additionally the blood immune parameters have been identified for each participant based on high-depth immunophenotyping (see XXX).
Genetic risk for developing Alzheimer’s Disease
The major risk for Alzheimer’s Disease is the APOE gene, especially the APOE Ɛ4 allele. Having one APOE Ɛ4 allele doubles or triples the risk of getting AD, having two APOE Ɛ4 alleles increases the risk even more, about eight to twelvefold. Besides this gene, approximately 70 other genetic risk loci were identified using genome-wide association studies. They can be combined in so-called polygenic risk scores (PRS), which may be used to estimate an individual’s lifetime genetic risk of disease.
The laboratory for complex genetics of the KU Leuven calculated AD PRS for the two in-house cohorts to select AD patients for inclusion in other parts of the PRISMA consortium. This selection is based on APOE genotype (E3/E3, E4/E4 and E3/E4) and PRS-AD, such that patients are selected from the low and high PRS end.
Publications
Luckett, E., Abakkouy, Y., Reinartz, M., Adamczuk, K., Schaeverbeke, J., Verstockt, S., De Meyer, S., Van Laere, K., Dupont, P., Cleynen, I., Vandenberghe, R. with Cleynen, I. (joint last author), Vandenberghe, R. (joint last author), Vandenberghe, R. (corresp. author) (2022). Association of Alzheimer’s disease polygenic risk scores with amyloid accumulation in cognitively intact older adults. Alzheimers Research & Therapy, 14 (1), Art.No. 138. doi: 10.1186/s13195-022-01079-4 Access via repository
Luckett, E., Abakkouy, Y., Schaeverbeke, J., Adamczuk, K., Van Laere, K., Dupont, P., Vandenberghe, R., Cleynen, I. (2021). Comparison of polygenic risk scores to predict amyloid accumulation in preclinical Alzheimer’s disease. In: NHAD program book. Presented at the New Horizons in Alzheimer's Disease, Leuven, Belgium