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2018 Grants - Petersen
Alzheimer's Disease Biomarker Combinations in the Community
Ronald C. Petersen, M.D.
2018 Zenith Fellows Award (ZEN)
How do toxic forms of tau and beta-amyloid interact to promote Alzheimer's disease?
Two key biomarkers (or biological factors) of Alzheimer's disease are the protein fragment beta-amyloid and the protein tau. These molecules become abnormal in the Alzheimer's brain and form harmful clumps called amyloid plaques and neurofibrillary tangles. Until recently, clinicians could only measure tau and beta-amyloid levels in a person with dementia once that person had died. We now, however, have two methods of measuring these pathologies in living individuals: imaging the brain with positron emission tomography (PET) scans and testing protein levels in cerebrospinal fluid (the fluid that surrounds the brain). Scientists are beginning to use these tools to reveal how tau and beta-amyloid may interact to increase Alzheimer's disease risk.
For their research grant, Ronald C. Petersen, M.D., and colleagues will use PET imaging and CSF testing to examine how brain health is affected by both tau and beta-amyloid clumping. The researchers will assess protein levels in about 3,000 older individuals from the Mayo Clinic Study of Aging. Most participants will begin the study with cognitively normal (healthy) brains or with mild cognitive impairment (MCI), a condition of subtle memory loss that often precedes Alzheimer's. These individuals will then be examined over time to determine how tau and beta-amyloid clumping — either alone or in combination — might influence whether the cognitively normal people develop MCI, or whether the people with MCI develop Alzheimer's disease.
Results of this study could shed new light on how cognitive decline occurs at the molecular level. The study could also provide important data for future clinical trials that seek to identify novel therapies for targeting tau, beta-amlyoid, or both.