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New study examines Alzheimer’s disease images and molecular biomarkers

May. 7, 2020, 10:00 AM


by Paul Govern

Alzheimer’s disease (AD) involves distinctive wasting away of certain brain regions, such that medical imaging of these regions can distinguish the disease from other subtypes of dementia.

A new study examines associations between various brain pathology biomarkers (measured in cerebrospinal fluid) and two magnetic resonance imaging (MRI) signatures of AD gray matter atrophy, identified within the past 11 years by research groups at Mayo Clinic and the University of California at San Diego. The study, led by researchers at Vanderbilt University Medical Center, appears in the journal Alzheimer’s and Dementia.

“To better understand what these imaging signatures might be telling us, we wanted to test their associations with select biomarkers and see whether the associations change in individuals at higher risk for AD, compared to healthy people with lower risk,” said the paper’s senior author, Angela Jefferson, PhD, professor of Neurology and director of the Vanderbilt Memory and Alzheimer’s Center.

Known risks for AD include advanced age, female sex and a genetic variant carried by 14% of the world’s population, APOE-ε4. The protein encoded by the APOE gene is involved in the metabolism of fats in the body and supports lipid transport and injury repair in the brain.

The study included 153 participants from the Vanderbilt Memory and Aging Project, a longitudinal observational study investigating risk factors for abnormal brain aging. Individuals were 60 to 92 years old, some with normal cognition and some with mild cognitive impairment.

The biomarkers used in the study include those for core AD pathology, that is, amyloid beta and phosphorylated tau, as well as markers for three other pathologies commonly seen with AD: total tau, a marker of neurodegeneration; neurogranin, a marker of synaptic dysfunction; and neurofilament light, a marker of axonal injury.

“Our headline result suggests that, among community-dwelling older adults, phosphorylated tau, total tau, synaptic dysfunction and neuroaxonal injury are associated with AD-related atrophy measured on MRI. Importantly, phosphorylated tau and synaptic dysfunction associations are more prominent in females, providing insight into how disease biology may be different in women versus men,” said Katherine Gifford, PsyD, assistant professor of Neurology, who co-led the study with Elizabeth Moore, an MD/PhD student.

According to the authors, its association with AD-related atrophy marks neuroaxonal injury as a potential therapeutic target, to mitigate neurodegeneration and memory loss in AD.

Amyloid beta concentration bore no association with AD-related atrophy, suggesting it may not contribute to neurodegeneration in early stages of the disease. Age also did not affect associations between biomarkers and AD-related atrophy, and APOE-ε4 had only a small effect on associations.

Other Vanderbilt co-authors include Omair Khan, MAS, Dandan Liu, PhD, Kimberly Pechman, PhD, Lealani Acosta, MD, MPH, Susan Bell, MBBS, MSCI, Maxim Turchan, MS, Bennett Landman, PhD, and Timothy Hohman, PhD. They were joined by researchers from the University of Gothenburg, in Sweden.

The study was funded in part by the National Institutes of Health (AG034962, AG056534) and the Alzheimer’s Association.


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