Aging: Studying combinations of genetic mutations may hold promise to uncover specific biomarkers of Alzheimer's disease in humans

Capturing the genetic architecture of Alzheimer's disease is challenging because the interaction of genetic and non-genetic factors in the etiology of Alzheimer's disease is very complex, and studies have shown that Alzheimer's disease biomarkers may help improve the pathological characteristics of the disease and its genetic architecture; Most studies have focused on analysing the association between a single genetic mutation and Alzheimer's disease biomarkers, rather than exploring the key role
played by combinations of genetic mutations.

Recently, a study entitled "Associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease biomarkers" published in the international journal Aging, Scientists from Duke University and other institutions have analyzed the association between the APOE ε2 and APOE ε4 alleles and a polygenic map including rs429358 encoded by ε4; The association
between TOMM40 rs2075650 and APOC1 rs12721046 polymorphisms and cerebrospinal fluid (CSF) and plasma β amyloid (Aβ40 and Aβ42) and tau biomarkers was also revealed.

In this study, we used data from three studies to analyze the association between APOE ε2 and APOE ε4 alleles, as well as Alzheimer's disease risk differentiation compound genotypes containing rs429358, rs2075650 and rs12721046 SNPs, and Aβ40, Aβ42 and tau AD biomarkers measured in cerebrospinal fluid and plasma, the investigators said.
The three studies included the Alzheimer's Disease Neuroimaging Initiative Research Program (ADNI), the Ingestion Arteriosclerosis Risk Study Program (ARIC), and the Framingham Heart Research Program (FHS).

Studying the combination of genetic mutations may hopefully uncover special biomarkers of Alzheimer's
disease in humans.

Image source: Aging (2022).
DOI:10.
18632/aging.
204384

The results of this study support the association between ε4 alleles and Aβ42 and CSF tau in plasma and CSF, and the correlation between ε2 alleles and baseline Aβ42 measurements in CSF, rather than longitudinal measurements
。 The researchers found that the ε4 polygenic profiles confering higher and lower risk of Alzheimer's disease may have a different association with tau protein rather than Aβ42, and that the regulatory effects of TOMM40 and APOC1 mutants on the ε4 allele suggest underlying heritary mechanisms
by which Aβ and tau proteins may play different roles in the pathological manifestations of Alzheimer's disease.

Finally, the researchers suggest that the polygenic profiles that confer higher and lower risk of Alzheimer's disease may be associated differently with tau, and the other main result of this study is that the researchers analyzed the association between APOE ε2 and ε4 alleles and Aβ40, Aβ42, and tau biomarkers in these cohort studies
.
(Biovalley Bioon.
com)

Original source:

Alexander M.
Kulminski,Ethan Jain-Washburn,Elena Loiko,et al.
 Associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease biomarkers, Aging (2022).
DOI:10.
18632/aging.
204384