Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland.
Nat Aging. 2024 Sep;4(9):1263-1278. doi: 10.1038/s43587-024-00682-4. Epub 2024 Aug 14.
Infections have been associated with the incidence of Alzheimer 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 (Aβ, 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.
感染与阿尔茨海默病和相关痴呆的发病率有关，但这些关联的机制仍不清楚。我们采用多队列方法发现，流感、病毒、呼吸道和皮肤及皮下感染与长期痴呆风险增加有关。这些感染还与特定区域的脑容量损失有关，最常见于颞叶。我们在血浆中鉴定出 942 种免疫相关蛋白中的 260 种，这些蛋白在有感染史的个体中表达水平不同。在与感染相关的蛋白中，有 35 种可预测易受感染性萎缩影响的脑区的体积变化。其中一些蛋白，包括 PIK3CG、PACSIN2 和 PRKCB，与认知能力下降和痴呆症的血浆生物标志物（Aβ、GFAP、NfL、pTau-181）有关。影响免疫相关感染相关蛋白表达的遗传变异，包括 ITGB6 和 TLR5，可预测脑容量损失。我们的研究结果支持感染在痴呆风险中的作用，并确定了感染可能导致神经退行性变的分子介质。
