Immune boosting to combat Alzheimer's disease: Position statement.

The societal cost of Alzheimer's disease (AD) and related dementias is immense, but there are no effective treatments. Emerging evidence suggests that AD brain pathology may be triggered by microbial infection, and that the diagnostic protein deposits in AD brain represent an antimicrobial defense mechanism. This raises the prospect of protection against AD through stimulation of the immune system. Specifically, non-specific activation through 'trained immunity' or 'immunopotentiation' is now known to offer protection against unrelated pathogens as well as against diverse diseases. Earlier findings that vaccine recipients are at reduced risk of developing AD have now been replicated around the world. Protection has been reported for diverse types of vaccines, and the effect sizes are clinically meaningful. Although these studies are predominantly observational, and are thus at risk of confounders such as 'healthy vaccinee' bias, several studies based on 'natural experiments' avoid this bias and provide stronger evidence that vaccine administration can reduce dementia risk. Most such vaccines can be obtained for a few dollars, although others are a little more expensive. But the cost of vaccination is entirely trivial compared to the financial burden of AD. Both clinical trials of immunopotentiation in AD and further research into the underlying mechanisms will be essential. This Position Statement briefly summarizes current knowledge and recommends that immune boosting should be placed at the top of the AD public health R&D agenda.