First, use of recently discovered genetic risk loci and more liberal significance thresholds for the GRS-contributing SNPs82–84 could help elucidate the clinical symptoms and underlying neural circuitry linked to accelerated brain ageing as a function of MDD and/or APOE vs no-APOE AD risk (e.g., anhedonia85,86; sleep disturbances87). This evidence concerns the gene APOE and Alzheimer disease.