The following is a summary of “Study of Alzheimer’s disease- and frontotemporal dementia-associated genes in the Cretan Aging Cohort,” published in the March 2023 issue of the Neurobiology of Aging by Mathioudakis et al.

The Cretan Aging Cohort (CAC) had 196 participants that were analyzed. 95 had Alzheimer’s disease (AD), 20 had MCI, and 81 had normal cognitive functions. The researcher’s studies were carried out using exome sequencing. Patients with Alzheimer’s disease were shown to have a higher frequency of the APOE 4 allele (23.2% versus 7.4% in controls; P < 0.01), while mutations in PSEN2 (p.Arg29His and p.Cys391Arg) were observed in 3% and 1% of AD and MCI patients, respectively. 

Two elderly patients with Alzheimer’s disease (AD) and two people outside the CAC with the amyotrophic lateral sclerosis/frontotemporal dementia (FTD) phenotype also had the TARDBP gene p.Ile383Val polymorphism that is associated with FTD. As a bonus, the p.Ser498Ala mutation in the favorably selected GLUD2 gene was less common in AD patients (2.11%) than in controls (16%; P <  0.01), suggesting that it may have a protective effect. 

While a similar trend was also found in another local replication cohort (n = 406) and a subset of the ADNI cohort (n = 808), neither sample size was large enough to reach statistical significance; thus, the results should be considered exploratory at best. The researcher’s results show the value of genetic testing for examining the aging population with the AD phenotype.

Source: sciencedirect.com/science/article/abs/pii/S0197458022001464