It is unknown how neuroinflammation may feature in the etiology of Alzheimer’s disease (AD). We profiled acute phase response (APR) proteins (α1-antitrypsin, α1-antichymotrypsin, ceruloplasmin, complement C3, ferritin, α-fibrinogen, β-fibrinogen, γ-fibrinogen, haptoglobin, hemopexin) in CSF of 1291 subjects along the clinical and biomarker spectrum of AD to investigate the association between inflammatory changes, disease outcomes, and demographic variables. Subjects were stratified by Aβ₄₂/t-tau as well as the following clinical diagnoses: cognitively normal (CN); subjective cognitive decline (SCD); mild cognitive impairment (MCI); and AD dementia. In separate multiple regressions (adjusting for diagnosis, age, sex, APOE-ε4) of each APR protein and a composite of all APR proteins, CSF Aβ₄₂/t-tau status was associated with elevated ferritin, but not any other APR protein in CN and SCD subjects. Rather, the APR was elevated along with symptomatic progression (CN < SCD < MCI < AD), and this was elevation was mediated by CSF p-tau181. APOE ε4 status did not affect levels of any APR proteins in CSF, while these were elevated in males and with increased age. The performance of the APR in predicting clinical diagnosis was influenced by APOE ε4 status, sex, and age. These data provide new insight into inflammatory changes in AD and how this intersects with pathology changes and patient demographics.

目前尚不清楚神经炎症在阿尔茨海默病 (AD) 的病因学中有何特征。我们分析了 1291 名受试者在临床和AD 的生物标志物谱，以研究炎症变化、疾病​​结果和人口统计学变量之间的关联。根据 Aβ ₄₂ /t-tau 以及以下临床诊断对受试者进行分层：认知正常 (CN)；主观认知衰退（SCD）；轻度认知障碍（MCI）；和 AD 痴呆。在单独的多元回归中（根据诊断、年龄、性别、APOE 进行调整）-ε4) 的每个 APR 蛋白和所有 APR 蛋白的复合物，CSF Aβ ₄₂ /t-tau 状态与升高的铁蛋白有关，但与 CN 和 SCD 受试者中的任何其他 APR 蛋白无关。相反，APR 随症状进展而升高（CN < SCD < MCI < AD），这是由 CSF p-tau181 介导的升高。APOE ε4 状态不影响脑脊液中任何 APR 蛋白的水平，而这些在男性和年龄增长中升高。APR 在预测临床诊断方面的表现受APOE ε4 状态、性别和年龄的影响。这些数据提供了对 AD 炎症变化以及它如何与病理变化和患者人口统计数据相交的新见解。