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Biomarker Changes during 20 Years Preceding Alzheimer's Disease
Jianping Jia1, Yuye Ning1, Meilin Chen1
1From the Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital (J.J., Y.N., M.C., Shuheng Wang, H.Y., F. Li, J.D., Yan Li, B.Z., W.Q., Q.W., Ying Li), Beijing Key Laboratory of Geriatric Cognitive Disorders, Clinical Center for Neurodegenerative Disease and Memory Impairment (J.J.), the Center of Alzheimer's Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders (J.J.), and the Department of Neurology, Beijing Anding Hospital (Y.W.), Capital Medical University, Key Laboratory of Neurodegenerative Diseases, Ministry of Education (J.J.), the Center for Cognitive Disorders, Beijing Geriatric Hospital (J.L.), and the Department of Neurology, Beijing Jishuitan Hospital (X.Y.), Beijing, the Department of Neurology, Daqing Oilfield General Hospital, Daqing (S.Y.), the Department of Neurology, the 960th Hospital of the People's Liberation Army, Jinan (J.Z.), the Department of Neurology, Baotou Central Hospital, Baotou (F. Liang), the Department of Psychiatry, Zhejiang Provincial People's Hospital, Hangzhou (Z.L.), and the Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang (Shan Wang) - all in China.
Alzheimer's disease biomarkers like amyloid-beta and tau began changing up to 18 years before diagnosis in Chinese adults. These changes in cerebrospinal fluid (CSF) biomarkers and brain imaging preceded cognitive decline, offering insights into early Alzheimer's disease progression.
Area of Science:
- Neuroscience
- Biomarker Research
- Gerontology
Background:
- Longitudinal studies on biomarker changes preceding Alzheimer's disease (AD) diagnosis are limited.
- Understanding the preclinical phase of sporadic AD is crucial for early intervention.
Purpose of the Study:
- To investigate the temporal trajectories of cerebrospinal fluid (CSF) biomarkers, cognitive function, and brain imaging in relation to Alzheimer's disease development.
- To determine the time course and order of biomarker abnormalities before clinical diagnosis.
Main Methods:
- A multicenter, nested case-control study involving cognitively normal participants from the China Cognition and Aging Study (2000-2020).
- Matched 648 AD cases with 648 cognitively normal controls, analyzing CSF biomarkers, cognitive tests, and brain imaging over a median follow-up of 19.9 years.
Main Results:
- Biomarkers diverged from normal levels years before diagnosis: amyloid-beta (Aβ)42 at 18 years, Aβ42/Aβ40 ratio at 14 years, p-tau181 at 11 years, total tau at 10 years, neurofilament light chain at 9 years, hippocampal volume at 8 years, and cognitive decline at 6 years.
- CSF biomarker changes initially accelerated and then slowed as cognitive impairment progressed.
Conclusions:
- This study elucidates the preclinical timeline of biomarker changes in sporadic Alzheimer's disease among Chinese participants.
- The findings provide a detailed temporal map of biomarker abnormalities preceding clinical diagnosis, aiding in understanding disease pathogenesis and timing interventions.
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