L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Alzheimers Dement. 2024 Mar;20(3):1753-1770. doi: 10.1002/alz.13560. Epub 2023 Dec 17.
We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases.
Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ) were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD).
GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ .
GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.
我们研究了新型血浆生物标志物是否与认知、认知能力下降以及神经退行性疾病中的日常生活活动的功能独立性有关。
使用超灵敏 Simoa 免疫分析,在 44 名健康对照者和 480 名被诊断为阿尔茨海默病/轻度认知障碍(AD/MCI)、帕金森病(PD)、额颞叶痴呆(FTD)谱系障碍或脑血管病(CVD)的患者中测量了胶质纤维酸性蛋白(GFAP)、神经丝轻链(NfL)、磷酸化 tau181(p-tau181)和淀粉样β(Aβ)。
与对照组相比,所有疾病的 GFAP、NfL 和/或 p-tau181 均升高,且与基线认知表现较差、认知下降较大和/或功能独立性较低广泛相关。虽然 GFAP、NfL 和 p-tau181 在所有疾病中均具有高度预测性,但 p-tau181 对 AD/MCI 队列更具特异性。在 FTD 和 CVD 队列中以及 Aβ中发现稀疏关联。
GFAP、NfL 和 p-tau181 是常见神经退行性疾病中认知和功能的有价值的预测因子,在专门的诊所和临床试验中可能有用。