2023 Zenith Fellows Award Program (ZEN)

Clinical Relevance of Novel Biomarkers for Tau and Alpha-Synuclein Pathology

How might new blood-based biomarkers help diagnose Alzheimer’s earlier?

Oskar Hansson, M.D.,Ph.D.
Lund University
Lund, Sweden

Background

Alzheimer’s is a progressive disease, and because of this, scientists are looking for ways to detect and diagnose it at an early asymptomatic stage, before memory loss and other cognitive changes become evident. Emerging methods of diagnosing Alzheimer’s involve measurements of biological markers (or biomarkers) such as the levels of tau or beta-amyloid (changes in these proteins are hallmark brain changes in Alzheimer’s). These methods often involve using positron emission tomography (PET) brain scans or collecting samples of cerebrospinal fluid (CSF, the biological fluid surrounding the brain and spinal cord). Such methods are invasive, and they may not detect disease at a sufficiently early stage.
Early diagnosis of Alzheimer’s is also complicated because of potential co-occurring brain diseases. For example, vascular (blood vessel) diseases, such as cerebral small vessel disease (CSVD), may impact an individual’s risk for brain diseases, including Alzheimer’s.  In addition, the symptoms and biological brain changes associated with other neurodegenerative disorders sometimes overlap with Alzheimer’s-associated changes. For instance, dementia with Lewy bodies is a neurodegenerative disorder characterized by the presence of protein clumps in the brain known as Lewy bodies; the primary component of these clumps is a protein known as alpha synuclein. 

These features are also observed in some individuals with Alzheimer's and in most individuals with Parkinson's disease. However, early diagnosis of dementia with Lewy bodies and Parkinson’s disease remains challenging due to a lack of available biomarkers. 

Research Plan

To overcome these challenges, Dr. Oskar Hansson and colleagues are developing blood-based biomarkers for early and accurate detection of Alzheimer’s-associated tau tangles, as well as important co-occurring brain diseases, such as CSVD and Lewy body dementia. The researchers will use two large studies that consist of data from more than 2,500 individuals including clinical assessments, blood and CSF samples, and PET brain scans. First, the team will develop and validate a blood-based biomarker for forms of the tau protein that can currently be detected in CSF samples. In addition, Dr. Hansson and colleagues will determine if misfolded alpha-synuclein (indicating Lewy bodies) can be detected in skin or blood samples, as well as in CSF. Finally, the team will develop novel blood-based biomarkers for CSVD.

Impact

If successful, this study may result in the development of new, blood-based biomarkers for alpha-synuclein and other biological brain changes that may co-occur in Alzheimer’s. Such biomarkers may lead to more effective methods of diagnosing and treating dementia at their earliest stages, when therapies can be most effective.