@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} }