A retrospective study, done by Jarith Ebenau and Sven van der Lee, PhD students of Amsterdam Neuroscience, investigated the role of genes in Alzheimer’s Disease. Their findings give more inside into the possibility for individualized risk profiling for Alzheimer’s Disease (AD).

For a while, it has been known that tens of genes are involved with Alzheimer’s Disease (AD). However, we still don’t know how these genes play a role in brain damage caused by AD. Therefore, this research aimed to investigate the relationship between the brain damage caused by AD and the genetic risk factors of AD.

This study retrospectively studied 829 cognitively normal individuals with Subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort and SCIENCe project. Jarith Ebenau and his colleagues rated each patient according to the amyloid/tau/neurodegeneration system (ATN), measured through CSF, PET-scans, and MRI-scans, which resulted in eight possible biomarker combinations. For over half of these individuals, biomarkers and follow-up assessments were available. With this data, the associations between the genetic variants and ATN biomarkers were examined. Next to this, they also evaluated the predictive value for incident dementia. Based on the 39 known genetic variants, the polygenic risk score (PRS) was calculated. The APOE gene was analyzed separately and was not included in the PRS.

The main finding of this study is that an AD PRS predicts biomarker pathology independently of APOE. Furthermore, APOE E e4 and the PRS were associated with the risk of AD dementia. A high PRS in combination with APOE e4 increased the risk of AD dementia, while a low PRS attenuated the risk associated with the e4 carriers.

To date, genetic information is not used in a clinical setting. Although the e4 allele is associated with a higher risk of dementia, this does not translate to all individuals. This study showed that considering all genetic variants associated with AD results in a more accurate estimate of future AD dementia. In the future, PRS might be implemented in individualized risk profiling. This is especially relevant for individuals with worries about memory presenting in the memory clinic.

Read the publication: Risk of dementia in APOE ε4 carriers is mitigated by a polygenic risk score

Source: Alzheimer Center Amsterdam