Neuropathology Core
The Neuropathology (NP) Core of the North Texas Alzheimer's Disease Research Center (NT-ADRC) facilitates innovative research into the overall theme of the NT-ADRC by:
- Studying the neuropathologic effects of cardiometabolic and protein seeding factors on the development of Alzheimer's disease and AD-related dementias (AD/ADRD)
- Assessing the accuracy and predictive value of antemortem biomarkers
- Assisting in identification of targets for disease prevention and management
The major focus of the NP Core is to fully characterize and document the structural neuropathologic features of AD and ADRD and other morphologic changes associated with aging and cognitive impairment in brains of subjects who come to autopsy.
Specific functions of the NP Core include:
- Collecting, preparing, and evaluating postmortem brain tissue from deceased AD/ADRD, mild cognitive impairment (MCI), and control subjects for use in diagnosis and research
- Reporting diagnostic information to physicians, families, and authorized researchers, and contributing diagnostic and related information to the National Alzheimer's Coordinating Center (NACC) database
- Collaborating with the Clinical Core to conduct Clinicopathologic Conferences for autopsy subjects
- Enhancing brain donation from underrepresented communities through collaboration with the Outreach, Recruitment, and Engagement (ORE) Core
The NP Core also supports investigator-initiated research on MCI, AD/ADRD, and aging by UT Southwestern researchers and external collaborators. We provide well-characterized tissue samples, neuropathologic diagnostic data, and derivative resources (e.g., digital images) to support ongoing projects, as well as offering research support to ADRC-funded developmental projects, REC Scholars, and other internal and external collaborators.
In keeping with the vascular theme of the NT-ADRC, the NP Core leverages the experience of investigators to develop new machine learning (ML) approaches to studying vascular contributions to AD/ADRD. Specifically, we use ML approaches to characterize pathological changes in digital images of autopsy brains to identify vascular-related morphologic alterations as well as develop algorithms to characterize features of amyloid angiopathy to predict risk of complications of anti-amyloid therapy in human subjects.
Education and Training
The NP Core provides a rich training environment for students, fellows, and junior faculty to acquire skills and experience in interdisciplinary research. Neuropathology fellows participate in the evaluation of all NP Core autopsy cases, present regularly at our highly popular interdisciplinary ADRC Clinicopathologic Correlation Conferences (CPCs), and are directly involved in research projects associated with the ADRC. The NP Core is also instrumental in the training of REC scholars in neuropathologic approaches to AD/ADRD research.
Innovations
The standard approach to neuropathologic characterization of AD and ADRD still depends primarily on traditional morphologic methods and human interpretation by light microscopy. We seek to enhance the neuropathologic phenotyping of human autopsy brains using novel methods of analysis. The most important of these is expanding the role of digital neuropathology, including the use of ML approaches, to better characterize structural features of neurodegeneration.
In 2013, the Neuropathology Brain Bank became one of the first neurodegenerative disease autopsy centers to incorporate the creation of whole slide images (WSIs) from autopsy cases into its workflow. We currently have a library of thousands of WSIs that have been used successfully in diagnostic, research, and educational endeavors.
For example, NP Core investigators used our WSI library to develop a deep learning model to identify neuropathologic features that accurately discriminate different tauopathies in tissue sections. A key aspect of such models is their ability to go beyond preconceived notions of which pathologic features have the greatest disease relevance, to identify features that might be nearly impossible to quantify via manual inspection, and which can lead to novel approaches to better understand neurodegeneration.
Collaborations
NP Core investigators interact broadly with all other ADRC components, including:
- Participating in the Administrative Core as part of the Core Leaders group
- Interacting with the Clinical Core and Biomarker and Imaging Core to coordinate monthly CPCs and other clinical, educational, and research efforts
- Serving as a quality control feedback mechanism for the Clinical Core and the Biomarker and Imaging Core
- Working closely with the Data Management, Informatics, and Statistics Core to ensure timely and accurate collection of neuropathology data, and to develop and maintain a web-based biospecimen locator for use by investigators who wish to access NP Core resources.
- Assisting the ORE Core in developing teaching materials regarding autopsy services
- Participating in CPCs, journal clubs, and other seminars sponsored by the ADRC
Core Faculty
- Core Lead
- Professor & Director of Neuropathology
Alzheimer's Disease Center - UT Southwestern Medical Center
- Assistant Professor of Pathology
- UT Southwestern Medical Center
- Assistant Professor of Biomedical Engineering
- UT Southwestern Medical Center