Melissa E. Murray, Ph.D., and her colleagues in Mayo Clinic's Translational Neuropathology Lab, use a multidisciplinary approach that integrates neuropathology, neuroimaging and genetics to investigate neurocognitive disorders (Alzheimer's disease), parkinsonian disorders (dementia with Lewy bodies) and motor neuron disorders (Lou Gehrig's disease). Dr. Murray is specifically interested in the effect of brain aging overlaid with a neurodegenerative disorder. The lab has revealed striking differences regarding vulnerability or resilience in affected individuals, especially in the setting of Alzheimer's disease (AD).

Focus areas

• Atypical Alzheimer's disease. The nature of patterns is what first drew Dr. Murray to the fields of neuroimaging and neuropathology. The changing shape of the hippocampus is a useful pattern utilized as a biomarker in AD. What became evident from neuropathologic studies, however, is that not all AD cases have an affected hippocampus.
• Neuroimaging of Alzheimer's disease. As a neuropathologist, Dr. Murray's studies intervene at patients' or study participants' last time-point (autopsy). However, there is much information that could be used to benefit living patients by understanding the neuropathologic underpinnings of neuroimaging changes.
• Neuroimaging and neuropathology of dementia with Lewy bodies. The second most common form of dementia is dementia with Lewy bodies, which is typically associated with Lewy body disease and mild AD neuropathologic changes. Given the overlap between the two neuropathologies, Dr. Murray and colleagues aim to supplement the lack of information regarding the extent to which AD may modify the clinical phenotype.
• Understanding clinicopathologic impact of cerebrovascular disease in the aging brain. Dr. Murray's early publications were directly related to investigating cerebrovascular disease as it relates to cognitive decline and neuropathologic changes in the brain.
• Neuropathology of tauopathies and TDP-43 proteinopathies. Having achieved a better understanding of the aging brain outside the setting of neurodegeneration, Dr. Murray re-focused her efforts in order to investigate the brain within the setting of dementia. Tau pathology outside the setting of amyloid-β is neuropathologically distinct from Alzheimer's disease with respect to the involvement of glia.

Significance to patient care

Dr. Murray's research seeks to improve diagnostic clinical accuracy through work with neurologists and radiologists. By carefully observing changes in the brain related to specific diseases, stereotypical patterns are evident. There are, however, groups of individuals whose disease pattern is far different, which often leads to an inaccurate diagnosis.

Overall, Dr. Murray's goal is to identify predictors of atypical patterns to assist neurologists with clinical interpretation and radiologists with neuroimaging interpretation. Dr. Murray is currently undertaking a genetic study to identify gene changes that lead to heightened susceptibility or resilience within the brains of patients in order to identify biological mechanisms that contribute to atypical disease patterns.