Certain patients with type 2 diabetes (T2D) may have specific genetic risk factors that put them at higher risk for developing Alzheimer’s disease (AD), according to a study conducted at and published recently in Molecular Aspects of Medicine.
Researchers led by Giulio Maria Pasinetti, MD, PhD, of the Icahn School of Medicine at Mount Sinai used recent genome wide association study (GWAS) findings to investigate whether T2D and AD share common genetic etiological factors and the potential impact of these genetic factors on the cellular and molecular mechanisms that may contribute to the development of both these diseases.
GWAS look at differences at many points in the genetic code to see if, across a population, one or more variations in the code are found more often in those with a given trait (for example, high risk for a disease). Even the smallest genetic variations — called single nucleotide polymorphisms (SNPs) — can have a major impact on a trait by swapping just one of the 3.2 billion “letters” that make up the human DNA code.
The researchers retrieved SNPs associated with T2D and AD from large-scale GWAS meta-analysis and tested for any overlap. “We then explored the function of the shared T2D/AD GWAS SNPs by leveraging expressional quantitative trait loci, pathways, gene ontology data, and co-expression networks,” they write. “We found 927 SNPs associated with both AD and T2D with p-value ≤0.01, an overlap significantly larger than random chance (overlapping p-value of 6.93E-28). Among these, 395 of the shared GWAS SNPs have the same risk allele for AD and T2D, suggesting common pathogenic mechanisms underlying the development of both AD and T2D.”
The authors conclude that their study tentatively supports epidemiological observation of disease concordance between T2D and AD. “Moreover,” they write,” the studies provide the much-needed information for the design of future novel therapeutic approaches, for a subpopulation of T2D subjects with genetic disposition to AD, that could benefit T2D and reduce the risk for subsequent development of AD.”
“We identified multiple genetic differences in terms of SNPs that are associated with higher susceptibility to develop type 2 diabetes as well as Alzheimer’s disease,” Pasinetti says. “Many of these SNPs are traced to genes whose anomalies are known to contribute to T2D and AD, suggesting that certain diabetic patients with these genetic differences are at high risk for developing Alzheimer’s. Our data highlights the need for further exploration of genetic susceptibility to Alzheimer’s disease in patients with T2D.”