**: People's Health Client.
On February 22, Jia Jianping's team from Xuanwu Hospital of Capital Medical University published an article entitled "Biomarker Changes During 20 Years Preceding Alzheimer's Disease" in the New England Journal of Medicine. For the first time, the dynamic changes of cerebrospinal fluid and imaging biomarkers in the asymptomatic to symptomatic stages of Alzheimer's disease were revealed, and the earliest key nodes of physiological and pathological changes in the onset of Alzheimer's disease were elucidated in detail, which provided time window guidance for the development of new drugs, and also provided strong evidence for ultra-early diagnosis and precise intervention.
It is reported that this is the world's largest and longest follow-up longitudinal cohort study reflecting changes in biomarkers before Alzheimer's diagnosis, which has been observed in the Chinese population for 20 years.
Alzheimer's disease is usually divided into familial Alzheimer's disease (FAD) and sporadic Alzheimer's disease (SAD). Compared with FAD, which has clear genetic evidence to be found, the timing and onset of SAD are more difficult**, and the study of biomarker changes requires a larger cohort and longer follow-up time, which makes it more challenging to achieve precise prevention and control of SAD.
Since 2000, more than 30,000 participants have undergone cerebrospinal fluid examinations, cognitive assessments, and brain imaging examinations every 2 to 3 years until they are diagnosed with Alzheimer's disease, die, lost to follow-up, withdrawn, or until the endpoint of the study. A total of 648 participants who developed Alzheimer's disease were included with a matched 648 participants with persistently normal cognition, and the temporal trajectories of changes in Alzheimer's disease-related cerebrospinal fluid biomarkers were compared between the two groups. The results of the study showed that the order and time points of biomarker differences between the Alzheimer's disease group and the cognitively normal group were A: A (18 years before diagnosis), A 42 40 (14 years before diagnosis), P-Tau 181 (11 years before diagnosis), T-Tau (10 years before diagnosis), NFL (9 years before diagnosis), hippocampal atrophy (8 years before diagnosis), and cognitive decline (6 years before diagnosis).
The study also found that with cognitive decline, the rate of change in the cerebrospinal fluid of patients with Alzheimer's disease A42 and A42 40 initially accelerated significantly, peaking around the time of a Mini-Mental State Scale (MMSE) score of 25 and a logical memory score of 11. Subsequently, the rate of change gradually slowed down, although the cognitive score decreased further, revealing the pattern of change between the cognitive level and peripheral markers.