Center for Protein Diagnostics (PRODI), Ruhr-University Bochum, Bochum, Germany.
Department of Biophysics, Ruhr-University Bochum, Bochum, Germany.
Alzheimers Dement. 2023 Mar;19(3):1020-1028. doi: 10.1002/alz.12745. Epub 2022 Jul 19.
Blood-based biomarkers for Alzheimer's disease (AD) are urgently needed. Here, four plasma biomarkers were measured at baseline in a community-based cohort followed over 17 years, and the association with clinical AD risk was determined.
Amyloid beta (Aβ) misfolding status as a structure-based biomarker as well as phosphorylated tau 181 (P-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) concentration levels were determined at baseline in heparin plasma from 68 participants who were diagnosed with AD and 240 controls without dementia diagnosis throughout follow-up.
Aβ misfolding exhibited high disease prediction accuracy of AD diagnosis within 17 years. Among the concentration markers, GFAP showed the best performance, followed by NfL and P-tau181. The combination of Aβ misfolding and GFAP increased the accuracy.
Aβ misfolding and GFAP showed a strong ability to predict clinical AD risk and may be important early AD risk markers. Aβ misfolding illustrated its potential as a prescreening tool for AD risk stratification in older adults.
目前迫切需要用于阿尔茨海默病（AD）的基于血液的生物标志物。在此，我们在一个基于社区的队列中测量了 4 种基线血浆生物标志物，并在超过 17 年的随访中确定了它们与临床 AD 风险的关联。
在基线时，我们使用肝素血浆测定了 68 名 AD 患者和 240 名未诊断为痴呆的对照组参与者的基于结构的生物标志物β淀粉样蛋白（Aβ）错误折叠状态以及磷酸化 tau181（P-tau181）、神经胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）浓度水平。
Aβ错误折叠在 17 年内对 AD 诊断具有较高的疾病预测准确性。在浓度标志物中，GFAP 的表现最佳，其次是 NfL 和 P-tau181。Aβ错误折叠和 GFAP 的组合提高了准确性。
Aβ错误折叠和 GFAP 具有较强的预测临床 AD 风险的能力，可能是重要的早期 AD 风险标志物。Aβ错误折叠显示出作为老年人 AD 风险分层的预筛选工具的潜力。
