PROJECT SUMMARY– NEUROPATHOLOGY CORE (NP) The primary goal of the Neuropathology Core is to collect post-mortem specimens from well-characterized participants (after receiving their consent), diagnose pathologic changes in their brains as precisely as possible, and share material and data freely. By accomplishing this goal, the Neuropathology Core aligns with the overall theme of the NM ADRC on understanding vascular and inflammatory contributions to Alzheimer's and cerebrovascular diseases in underrepresented groups in New Mexico. The core is led by two neuropathologists with complementary expertise (Elaine L. Bearer, MD-PhD, and Karen SantaCruz, MD). The participants are both younger and older people who have multiple causes of dementia with well-characterized evidence of neuro- inflammation, AD and vascular protein abnormalities; and the New Mexico population includes rural low-income residents and a majority minority population (50% Hispanic/Latinx and 10% American Indians, living on Pueblos and Reservations).The Neuropathology Core will have access to the UNM Brain Bank with over 265 archival brains, including blocks and slides from this population, and is positioned to collect brains prospectively from study participants who had ante-mortem neuro- and vascular imaging, CSF biomarker measurements, and cognitive tests, as well as from age-matched community members with or without dementia. All donors are consented, and autopsies performed at the top-ranking New Mexico Office of Medical Investigator. The Neuropathology Core will continue to work closely with the other cores of NM ADRC. Significance of this core’s contributions include: i) Acquisition from under-represented populations; ii) Focus on white matter, vascular and inflammatory disease. Our Innovations include: i) Ante-mortem/post-mortem MR imaging with co-registrations and pathology correlates; (ii) development of double-label IHC; and (iii) spatial transcriptomics at high, subcellular, resolution. Specific aims are four-fold: 1) Acquire, dissect, diagnose, store, and share post-mortem materials; 2) Develop histopathological strategies to assess vascular and inflammatory biomarkers; 3) Explore spatial transcriptomics of cognitive impairment in AD and VCID; 4) Develop bidirectional interactive teaching materials to educate the public and ourselves on the cultural and scientific value of AD research. Resultant well- characterized biological material, data, generalizable protocols and novel teaching materials will be shared broadly to investigators both at and beyond UNM, for work aimed at translating what we have learned about progression-related biomarkers as intervention targets, and to further promote community engagement.