Research
Neuropathology of 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 Alzheimer's disease. What became evident from neuropathologic studies, however, is that not all Alzheimer's disease cases have an affected hippocampus.
To objectively capture Alzheimer's disease subtypes, Dr. Murray designed a mathematical algorithm. Three subtypes emerged with striking demographic and clinical differences. Using advanced digital pathology techniques, the Translational Neuropathology Lab is investigating the relationship with coexisting neuropathologies, such as vascular disease and the overall effect on the death of a neuron. The lab has discovered evidence that supports the differential involvement of the cholinergic system across Alzheimer's disease subtypes, and that evidence may have therapeutic implications.
Funding from the National Institute on Aging supports this work.
Neuroimaging of Alzheimer's disease
As a neuropathologist, Dr. Murray's studies intervene at study participants' last time-point (autopsy). However, there is much information that can be used to benefit people living with Alzheimer's disease by understanding the neuropathologic underpinnings of neuroimaging changes. Ongoing projects are investigating the target of multimodal imaging modalities, including tau positron emission tomography and structural magnetic resonance imaging. The overall goal is to design an imaging-based algorithm that recapitulates the neuropathologic patterns toward the effort of earlier diagnosis of atypical Alzheimer's disease.
Funding from the National Institute on Aging supports this work.
Selective vulnerability of the hippocampus
Using digital pathology and gene expression techniques, the Translational Neuropathology Lab's goal is to discover the genetic underpinnings of hippocampal involvement in Alzheimer's disease. Our translational neuropathology approach bases the selection of genes on the relationship between quantitative neuropathology specific to Alzheimer's disease with gene expression of RNA transcripts derived from RNA-sequencing.
The lab has identified a set of 52 genes that the research team is interrogating using NanoString technology in a larger set of autopsy-confirmed Alzheimer's disease cases. The research team's goal is to translate these findings to a blood-based biomarker that would capture variability and improve signal-to-noise values to enable accurate prediction of disease course.
These studies have been largely supported by competitive foundation support and generous support from the Center for Individualized Medicine. Recently, the lab was awarded a research grant from the Alzheimer's Association to continue this investigation.
Florida Autopsied Multi-Ethnic (FLAME) cohort
The risk of developing Alzheimer's disease dementia is 1.5 times greater in Hispanic Americans compared with European Americans (white) and twice as high in African Americans (Black). Intriguingly, Dr. Murray's Translational Neuropathology Lab has found that Hispanic Americans live longer with the disease, suggesting that there may be unknown protective factors.
With one of the largest series of autopsy-confirmed Hispanic decedents having a neuropathologic diagnosis of Alzheimer's disease (n=85), the research team is investigating neurobiologic changes that may account for differences in survival. Using sophisticated technology to measure Alzheimer-related changes to proteins, researchers will be able to examine biological factors that may differ between Hispanic decedents and white decedents.
The Translational Neuropathology Lab also is exploring comparisons with Black decedents with Alzheimer's disease in a smaller cohort that is available (n=31). With a much larger cohort of white decedents (n=2651), the research team will be able to match case to case for important factors, such as age at death, sex and education.
Ongoing efforts are underway to carefully review clinical history for measures of cognitive reserve by examining evidence of bilingualism and converting occupation to a job level score, as recommended by statistics from the Department of Labor. These efforts will provide one of the first translational neuropathology studies to specifically examine the survival of Hispanic Americans with Alzheimer's disease.