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Repurposing of existing vaccines for personalized prevention of Alzheimer’s disease: Vaccination against pneumonia may reduce AD risk depending on genotype
Author(s) -
Ukraintseva Svetlana,
Yashkin Arseniy,
Duan Matt,
Akushevich Igor,
Arbeev Konstantin,
Wu Deqing,
Stallard Eric,
Tropsha Alex,
Yashin Anatoliy
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046751
Subject(s) - medicine , vaccination , pneumonia , disease , risk factor , cohort , dementia , repurposing , genotype , immunology , biology , gene , biochemistry , ecology
Abstract Background Repurposing of existing vaccines could be a promising approach to Alzheimer’s disease (AD) prevention, exploiting potential heterologous effects of such vaccines. Adult vaccinations against pneumonia and the flu showed beneficial off‐target effects on mortality and morbidity in some studies, including on dementia‐related outcomes, suggesting that respective vaccines may be evaluated as repurposing candidates for prevention of AD and/or other dementias. Method We investigated associations between pneumococcal vaccine, with and without an accompanying flu shot, and the risk of AD among 5,146 elderly participants (65+) of the Cardiovascular Health Study, using covariates including sex, race, birth cohort, education, smoking, and rs2075650, a known genetic risk factor for AD in TOMM40 gene that may also be involved in brain vulnerability to infection through its connection to NECTIN2 (Yashin et al. 2018). Result Being vaccinated against pneumonia between ages 65‐75 was associated with a reduction in the risk of AD afterwards (OR = 0.70; P < 0.04) in logistic model with all covariates. A largest reduction in the risk of AD (OR = 0.62; P < 0.04) was observed in the vaccinated against pneumonia non‐carriers of rs2075650 G allele (risk factor for AD). Total count of vaccinations against pneumonia and the flu between ages 65 and 75 was also associated with a lower risk of AD occurrence later in life (OR = 0.88; P < 0.01); however, the effect was not seen for the flu alone. Conclusion Vaccination against pneumonia before the age 75 may reduce AD risk later in life, especially in people without genetic risk factor for AD (rs2075650, G allele). These results suggest that pneumococcal vaccine may be a promising candidate for repurposing for personalized AD prevention in carriers of particular genotypes. Validation of these effects in higher power datasets is warranted. The study was in part supported by NIH grants R56AG059428, 1R01AG062623, and 2R01AG046860.