A range of evidence suggests that persistent infection, particularly some herpesviruses, raises the risk of Alzheimer's disease and other neurodegenerative conditions. It may be that Alzheimer's is strongly dependent on the dysfunction of immune cells in the brain, and infection hastens this dysfunction in later life. Equally, other less well understood mechanisms may be involved. Here, researchers demonstrate that it is possible to distinguish a protein expression signature of past infection in blood samples, and some of these differentially expressed proteins also correlate to measures of brain aging.
Infections have been associated with the incidence of Alzheimer's disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin, and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.
We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ42/40, GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.
Link: https://doi.org/10.1038/s43587-024-00682-4
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