01862nas a2200241 4500008004100000022001400041245007900055210006900134260000900203300001100212490000700223520116300230100002801393700001801421700001601439700001401455700002201469700002301491700002601514700002101540700002301561856003601584 2020 eng d a2352-872900aGenetic and regulatory architecture of Alzheimer's disease in the region.0 aGenetic and regulatory architecture of Alzheimers disease in the c2020 ae120080 v123 a

Introduction: Apolipoprotein E () ε2 and ε4 alleles encoded by rs7412 and rs429358 polymorphisms, respectively, are landmark contra and pro "risk" factors for Alzheimer'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.

1 aKulminski, Alexander, M1 aShu, Leonardo1 aLoika, Yury1 aHe, Liang1 aNazarian, Alireza1 aArbeev, Konstantin1 aUkraintseva, Svetlana1 aYashin, Anatoliy1 aCulminskaya, Irina uhttps://chs-nhlbi.org/node/8397