Plasma Amyloid-β, Total Tau, and Neurofilament Light Chain Across the Alzheimer’s Disease Clinical Spectrum: A Population-Based Study.

Oct 30, 2023

Experts: Yi Dong,Tingting Hou,Yuanjing Li,Rui Liu,Lin Cong,Keke Liu,Cuicui Liu,Xiaolei Han,Yifei Ren,Shi Tang,Bengt Winblad,Kaj Blennow,Yongxiang Wang,Yifeng Du,Chengxuan Qiu

Plasma biomarkers have emerged as a promising approach for characterizing pathophysiology in mild cognitive impairment (MCI) and Alzheimer’s disease (AD).
We aimed to characterize plasma biomarkers for AD and neurodegeneration across the AD clinical continuum, and to assess their ability to differentiate between AD, MCI, and normal cognition.
This population-based study engaged 1,446 rural-dwelling older adults (age ≥60 years, 61.0% women) derived from MIND-China; of these, 402 were defined with MCI and 142 with AD. Plasma amyloid-β (Aβ), total tau (t-tau), and neurofilament light chain (NfL) concentrations were analyzed using the Simoa platform. Data were analyzed using linear and logistic regression models, and receiver operating characteristic (ROC) analysis.
Across the AD clinical spectrum, plasma Aβ40 and NfL increased, whereas Aβ42/Aβ40 ratio decreased. Plasma t-tau was higher in people with AD dementia than those with MCI or normal cognition. Plasma NfL outperformed other biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75), but all plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC <0.60). Plasma NfL in combination with age, sex, education, and APOE genotype yielded the AUC of 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition.
In this Chinese population, AD plasma biomarkers vary by age, sex, and APOE genotype. Plasma Aβ, t-tau, and NfL differ across the AD clinical spectrum, and plasma NfL appears to be superior to plasma Aβ and t-tau for defining the clinical spectrum.

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ABOUT THE EXPERTS

Yi Dong,Tingting Hou,Yuanjing Li,Rui Liu,Lin Cong,Keke Liu,Cuicui Liu,Xiaolei Han,Yifei Ren,Shi Tang,Bengt Winblad,Kaj Blennow,Yongxiang Wang,Yifeng Du,Chengxuan Qiu

Yi Dong

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Tingting Hou

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Yuanjing Li

Aging Research Center and Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden.

Rui Liu

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Lin Cong

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Keke Liu

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Cuicui Liu

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Xiaolei Han

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Yifei Ren

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Shi Tang

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Bengt Winblad

Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.

Theme Inflammation and Aging, Karolinska University Hospital, Huddinge, Sweden.

Kaj Blennow

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Yongxiang Wang

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Aging Research Center and Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden.

Yifeng Du

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China.

Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging in Shandong First Medical University, Ministry of Education of the People’s Republic of China, Jinan, Shandong, P.R. China.

Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P.R. China.

Chengxuan Qiu

Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China.

Aging Research Center and Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden.