Chinese scientists reveal biomarker changes long before Alzheimer's diagnosis

Chinese scientists have made a new breakthrough by discovering biomarker changes predicting Alzheimer's disease (AD) long before clinical symptom onset in a 20-year study, shedding light on the progression of the disease, crucial for its early diagnosis and intervention.

Led by Professor Jia Jianping from Xuanwu Hospital of the Capital Medical University, the scientists conducted a multicenter, nested case-control study of AD biomarkers in about 30,000 cognitively normal participants between January 2000 and December 2020, tracking their testing of cerebrospinal fluid (CSF), cognitive assessments and brain imaging at two to three-year intervals.

They then compared the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging between 648 participants who eventually developed AD and 648 participants with normal cognition.

They found the CSF and imaging biomarkers in the AD group diverged from the other group at specific estimated numbers of years before diagnosis, with the changes of an Alzheimer's-linked protein occurring first, 18 years before diagnosis:

· amyloid-beta (Aβ)42, 18 years;

· the ratio of Aβ42 to Aβ40, 14 years;

· phosphorylated tau 181, 11 years;

· total tau, 10 years;

· neurofilament light chain, 9 years;

· hippocampal volume, 8 years;

· cognitive decline, 6 years.

"As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer's disease group initially accelerated and then slowed," they added.

Their research titled "Biomarker changes during 20 years preceding Alzheimer's disease" was published in The New England Journal of Medicine on Thursday.

The study's importance "cannot be overstated," Richard Mayeux, an Alzheimer's specialist at Columbia University, wrote in an accompanying editorial.

"Knowledge of the timing of these physiological events is critical" for testing new ways of treating and maybe eventually even preventing AD, he said.

"The more we know about viable Alzheimer's treatment targets and when to address them, the better and faster we will be able to develop new therapies and preventions," the Associated Press reported, citing Claire Sexton, the Alzheimer's Association's senior director of scientific programs.