@article {8397, title = {Genetic and regulatory architecture of Alzheimer{\textquoteright}s disease in the region.}, journal = {Alzheimers Dement (Amst)}, volume = {12}, year = {2020}, month = {2020}, pages = {e12008}, abstract = {

Introduction: Apolipoprotein E () ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro "risk" factors for Alzheimer{\textquoteright}s disease (AD).

Methods: We examined differences in linkage disequilibrium (LD) structures between (1) AD-affected and unaffected subjects and (2) older AD-unaffected and younger subjects in the 19q13.3 region harboring rs7412 and rs429358.

Results: AD is associated with sex-nonspecific heterogeneous patterns of decreased and increased LD of rs7412 and rs429358, respectively, with other polymorphisms from five genes in this region in AD-affected subjects. The LD patterns in older AD-unaffected subjects resembled those in younger individuals. Polarization of the ε4- and ε2 allele-related heterogeneous LD clusters differentiated cell types and implicated specific tissues in AD pathogenesis.

Discussion: Protection and predisposition to AD is characterized by an interplay of rs7412 and rs429358, with multiple polymorphisms in the 19q13.3 region in a tissue-specific manner, which is not driven by common evolutionary forces.

}, issn = {2352-8729}, doi = {10.1002/dad2.12008}, author = {Kulminski, Alexander M and Shu, Leonardo and Loika, Yury and He, Liang and Nazarian, Alireza and Arbeev, Konstantin and Ukraintseva, Svetlana and Yashin, Anatoliy and Culminskaya, Irina} } @article {9509, title = {Vaccination Against Pneumonia May Provide Genotype-Specific Protection Against Alzheimer{\textquoteright}s Disease.}, journal = {J Alzheimers Dis}, year = {2023}, month = {2023 Oct 03}, abstract = {

Vaccine repurposing that considers individual genotype may aid personalized prevention of Alzheimer{\textquoteright}s disease (AD). In this retrospective cohort study, we used Cardiovascular Health Study data to estimate associations of pneumococcal polysaccharide vaccine and flu shots received between ages 65-75 with AD onset at age 75 or older, taking into account rs6859 polymorphism in NECTIN2 gene (AD risk factor). Pneumococcal vaccine, and total count of vaccinations against pneumonia and flu, were associated with lower odds of AD in carriers of rs6859 A allele, but not in non-carriers. We conclude that pneumococcal polysaccharide vaccine is a promising candidate for genotype-tailored AD prevention.

}, issn = {1875-8908}, doi = {10.3233/JAD-230088}, author = {Ukraintseva, Svetlana and Duan, Matt and Simanek, Amanda M and Holmes, Rachel and Bagley, Olivia and Rajendrakumar, Aravind L and Yashkin, Arseniy P and Akushevich, Igor and Tropsha, Alexander and Whitson, Heather and Yashin, Anatoliy and Arbeev, Konstantin} }