Associations of infections and vaccines with Alzheimer's disease point to a role of compromised immunity rather than specific pathogen in AD.

Diverse pathogens (viral, bacterial, fungal) have been associated with Alzheimer's disease (AD) and related traits in various studies. This suggests that compromised immunity, rather than specific microbes, may play a role in AD by increasing an individual's vulnerability to various infections, which could contribute to neurodegeneration. If true, then vaccines that have heterologous effects on immunity, extending beyond protection against the targeted disease, may hold a potential for AD prevention. We evaluated the associations of common adult infections (herpes simplex, zoster (shingles), pneumonia, and recurrent mycoses), and vaccinations against shingles and pneumonia, with the risks of AD and other dementias in a pseudorandomized sample of the Health and Retirement Study (HRS). Shingles, pneumonia and mycoses, diagnosed between ages 65 and 75, were all associated with significantly increased risk of AD later in life, by 16 %–42 %. Pneumococcal and shingles vaccines administered between ages 65–75 were both associated with a significantly lower risk of AD, by 15 %–21 %. These effects became less pronounced when AD was combined with other dementias. Our findings suggest that both the pneumococcal polysaccharide vaccine and the live attenuated zoster vaccine can offer significant protection against AD. It remains to be determined if non-live shingles vaccine has a similar beneficial effect on AD. This study also found significant associations of various infections with the risk of AD, but not with the risks of other dementias. This indicates that vulnerability to infections may play a more significant role in AD than in other types of dementia, which warrants further investigation. • Shingles, pneumonia, and recurrent mycoses all increased risk of AD after age 75. • Vaccinations against shingles and pneumonia both significantly reduced risk of AD. • The associations with infections and vaccines were stronger for AD than for other dementias. • Results of this study point to a role of compromised immunity in AD. • Pneumococcal and zoster vaccines are promising candidates for repurposing in AD. [ABSTRACT FROM AUTHOR]