The New England Journal of MedicineBiomarker Changes during 20 Years Preceding Alzheimer’s Disease

Understanding the Precursors to Alzheimer’s: A 20-Year Biomarker Study

A study conducted over two decades provides valuable insights into the biomarker changes occurring years before the clinical diagnosis of Alzheimer’s disease. This research, centered on a Chinese cohort, delineates the temporal trajectory of various biomarkers, offering a deeper understanding of the preclinical phase of Alzheimer’s disease.

Study Design:

• Multi-center, nested case-control study within the China Cognition and Aging Study.
• Duration: January 2000 through December 2020 with 648 Alzheimer’s patients matched with 648 cognitively normal participants.
• Participants underwent cerebrospinal fluid (CSF) testing, cognitive assessments, and brain imaging at 2 to 3-year intervals.

Key Findings:

• Biomarker changes precede Alzheimer’s diagnosis by years: Aβ42 (18 years), Aβ42/Aβ40 ratio (14 years), phosphorylated tau 181 (11 years), total tau (10 years), neurofilament light chain (9 years), hippocampal volume (8 years), and cognitive decline (6 years).
• Initial acceleration followed by a slowdown in CSF biomarker level changes as cognitive impairment progresses in Alzheimer’s group.

HCN Medical Memo
This longitudinal study elucidates the progressive changes in CSF biomarkers over two decades before the clinical onset of Alzheimer’s disease, highlighting a distinct temporal divergence from normal cognitive trajectories.

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