Neuropath Core

Neuropathology Core – Project Summary The Neuropathology (NP) Core will provide unique resources to support the Wake Forest Alzheimer’s Disease Research Center (ADRC) focus on transitions from normal aging to MCI, AD, and related disorders, and the role of metabolic and vascular risk pathways in these transitions. The Core will foster innovative research in all areas relevant to AD. To accomplish these goals, the Core will provide state-of-the-art collection, storage, and distribution of brain and other biospecimens, establish neuropathological diagnoses of decedent Clinical Core (CC) participants, and provide resources and expertise for non-human primate (NHP) models for pivotal mechanistic and therapeutic research. The NP Core will also contribute to the ADRC theme of health disparities with a unique program focused on increasing brain donation from underrepresented groups (URGs). Through these activities, the NP Core will make impactful contributions to many National Alzheimer’s Project Act (NAPA) Research Milestones, such as supporting deep, longitudinal molecular endophenotyping of cohorts that include URGs (1A), data and sample sharing (3A, 4D), and development of the next generation of animal models (4A, B, C). The NP Core currently maintains a biospecimen repository of DNA, blood, and cerebrospinal fluid (CSF) from >1,100 well-characterized participants from the ADRC and its affiliated studies. In the coming cycle, we will continue to archive biospecimens from ADRC CC participants who have received careful metabolic and vascular characterization. DNA, CSF and blood will be provided to NCRAD, other consortia, and individual investigators. AD CSF biomarkers (Ab40, Ab42, tau, and p-tau181) are rigorously measured on all participants who undergo lumbar puncture (LP), and special expertise is available for blood and CSF biomarkers of metabolic and vascular disease. We continually assess scientific advances in identifying novel blood and CSF biomarkers of ADRD and will implement these as the field evolves. Further, human protocols for brain, blood and CSF collection have been applied to NHP models, creating a unique resource with which the AD research community can conduct pivotal translational research. In the past cycle, we demonstrated that our NHP model has neuropathologic changes similar to early AD such as amyloid plaques, AD-like CSF Ab42 profiles, cerebral hypometabolism, and reduced brain volumes. Consultation about NHP and other models (rodent, organoid) will be available. In summary, through careful clinico-pathologic analysis of well characterized cohorts, unique biospecimen repositories, and novel translational models, the NP Core will promote the WF ADRC themes, and provide an exceptional resource to investigate underlying mechanisms, novel biomarkers, and therapeutic targets that impact progression from normal aging to MCI and ADRD.