In a landmark paper published in the New England Journal of Medicine (NEJM), a team of Chinese researchers have mapped biomarker changes over time, identifying key signals that can precede a diagnosis of Alzheimer’s disease by over 18 years. There is a growing awareness that biological signs of Alzheimer’s disease (AD) can be detected many years before a person develops cognitive changes and symptoms. However, the specific sequence of biological changes over time has not been conclusively established, in part due to challenges in performing longitudinal studies over extensive periods of time.
To address this important issue, a team of researchers from the China Cognition and Aging Study (COAST) set out to map the biological changes that occur in the years and decades preceding AD diagnosis, by analysing samples of cerebrospinal fluid (CSF), brain imaging data, and cognitive test scores from COAST participants who were enrolled between the year 2000 and 2020. COAST was a China-wide, prospective cohort study that enrolled participants aged 45-65 years in 2000 with no cognitive complaints. The primary analysis reported in the NEJM paper focused on 648 COAST participants who developed AD, matched with 648 participants with normal cognition, following them for almost 20 years. By comparing CSF biomarker and brain imaging datasets between the two groups, the researchers were able to track when biomarker and brain imaging changes first appeared during the development of AD.
Levels of CSF amyloid beta (42) were the first to diverge, with changes detectable 18 years prior to diagnosis. Next, the ratio of CSF amyloid beta (42) to amyloid beta (40) was shown to be different 14 years prior to clinical signs of disease appearing, followed by changes in phosphorylated tau181 11 years before diagnosis. CSF levels of neurofilament light chain were altered 9 years before diagnosis, followed by hippocampal atrophy and cognitive decline a few years later. Together, these important results shine a light on the timing of biological events in the years prior to diagnosis, which could help clinicians better understand when to initiate efforts for risk reduction, prevention and therapy.
https://www.nejm.org/doi/full/10.1056/NEJMoa2310168?query=featured_home