Core D: Neuropathology Core

PROJECT SUMMARY/ABSTRACT – NEUROPATHOLOGY CORE The Neuropathology Core is an essential part of the Alzheimer's Disease Core Center (ADRC). During life, the signs and symptoms of Alzheimer's disease (AD) are not sufficiently different from several other conditions, resulting in misdiagnosis, even at the most advanced centers, in 25% or more of subjects, when newly developed imaging and biofluids biomarkers are not used. Even with such biomarkers, the presence of concurrent and clinically significant major pathologies is rarely detected. Examination of the brain after death by an experienced Neuropathologist allows the Center's research results to be appropriately interpreted. This is particularly important for our Center's overarching theme, to provide the resources needed to establish the accuracy of emerging blood-based biomarkers (BBBs) in the diagnosis of AD and related dementias (ADRD) and use them to detect, track, and study preclinical AD, including in persons from diverse backgrounds, and to find an effective AD prevention therapy by 2025. A second major role of the Neuropathology Core is to provide an extensive resource of rapidly autopsied, neuropathologically and molecularly characterized tissue for researchers inside and outside of Arizona, enabling them to discover the underlying molecular mechanisms of disease and design appropriate therapeutic interventions. A detailed understanding of the genomics and related molecular processes of disease pathogenesis, obtained by comparative study of diseased and non-diseased brain tissue is critical to finding such interventions. A third important goal of the Neuropathology Core is to support the Arizona ADRC's overarching theme and address National Alzheimer's Project Act (NAPA) Implementation Milestones.

Our Specific Aims: 1) To provide comprehensive neuropathological assessments and extremely precise neuropathologic diagnoses in ADRC Clinical Core and Affiliated Brain and Body Donation Program (BBDP) research participants who donate their brains after they die. 2) To provide an extensively shared resource of rapidly autopsied, high-quality neuropathologically characterized brain tissue and other body tissues for researchers to advance the study of AD/ADRD, support the study of molecular mechanisms, and therapeutic targets, including in those with AD and a wide range of ADRDs as well as cognitively unimpaired persons with and without preclinical AD. 3) To provide an extensively shared resource of ADRC and organizationally supported annual blood samples, neuropathological diagnoses, and data to help researchers inside and outside of Arizona evaluate promising BBBs for AD/ADRD in neuropathologically characterized brain donors by providing neuropathological validation of blood samples acquired in the last 1-2 years of life. The last aim is intended to support the role of BBBs in the diagnosis and preclinical detection, tracking and study of AD, the inclusion of under-represented Hispanic/Latino, Native American and other under-represented minority groups, help find an effective AD prevention therapy by 2025, and help fulfill National Alzheimer's Project Act (NAPA) goals.

Grant Number: 5P30AG072980-05
NIH Institute/Center: NIH
Principal Investigator: THOMAS BEACH