2022 Alzheimer's Association Clinical Scientist Fellowship to Promote Diversity (AACSF-D)

Plasma Biomarkers in the Continuum from Normal Cognition through MCI to AD

Can biomarkers in the blood be used to predict who will progress from mild memory changes?

Yongxiang Wang, M.D., Ph.D.
Shandong Provincial Hospital affiliated to Shandong First Medical University
Jinan, China

Background

Research suggests that the brain changes associated with Alzheimer’s and other dementias start decades before clinical signs are evident. Several emerging methods may allow detection of brain changes associated with Alzheimer’s in the cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord) before symptoms appear. This requires measuring specific biological markers, or “biomarkers,” from the CSF. These biomarkers include brain levels of beta-amyloid and tau (proteins that accumulate into plaques and tangles, hallmarks of brain changes observed in Alzheimer’s) and neurofilament light chain protein (NfL, a component of nerve cells that is indicative of injury to the nervous system).

While biomarkers in the CSF may show signs associated with Alzheimer’s before clinical symptoms arise, the collection of CSF is invasive, making this technique difficult to use in routine clinical exams. Some studies suggest that an alternative approach is examining biomarkers in blood samples. Researchers believe that identification of blood biomarkers associated with mild cognitive impairment (MCI, a state of subtle memory loss that may precede Alzheimer’s) could help improve prediction of which individuals are more likely to progress to dementia. However, blood biomarkers for predicting who may progress from mild memory changes to more advanced memory changes (dementia) is not fully understood.

Research Plan

Dr. Yongxiang Wang and colleagues will study whether blood biomarkers for Alzheimer’s and neurodegeneration in older adults can be used to differentiate cognitively unimpaired aging, mild cognitive impairment, and Alzheimer’s. The researchers will use data from the Multimodal Interventions to Delay Dementia and Disability in rural China study (MIND-China). They will collect data on clinical, neuropsychological, medical, and genetic data for 5,765 adults aged 60 years and older living in rural communities in western Shandong Province, China. The research team will use a state of the art technique to measure blood biomarkers for Alzheimer’s and neurodegeneration (levels of beta-amyloid, tau, and NfL) in over 1,000 individuals. The team will also conduct brain scans.
Dr. Wang and team will investigate the connection between blood biomarkers for mild memory changes and the more advanced memory changes, including Alzheimer’s. The researchers will also study how different interventions (including health and lifestyle interventions) may impact changes in blood biomarkers for Alzheimer’s and neurodegeneration.

Impact

The results of this project may help shed light on biological brain changes associated with Alzheimer’s and other brain diseases in a large population in China. If successful, the findings may be used to develop blood-based biomarkers to diagnose the risk of developing Alzheimer’s and other dementia.