University of Kansas Alzheimers Disease Center P30 Neuropathology supplement

PROJECT SUMMARY This Supplement requests one year of funding to support unforeseen costs associated with the University of Kansas Alzheimer’s Disease Research Center (KU ADRC) Neuropathology (NP) Core. The Neuropathology Core provides critical KU ADRC infrastructure in collaborating with other ADRC Cores

(Figure 1). The neuropathology core function is essential to the Center’s mission and scientific theme by 1) Maintaining the autopsy program and Brain Bank; 2) Providing neuropathologic diagnosis, consultation, and training for investigators and trainees; 3) Obtaining dural and skin biopsies for induced pluripotent stem cell

(IPSC) lines; and 4) Providing brain tissue for mitochondrial DNA (mtDNA) sequencing by the Biomarker Core. The NP Core continually upgrades it status to the diagnostic advances in the field and evolves according to the approved and accepted new guidelines, knowledge and state-of-the-art technology. Furthermore, the Core also

participates in the important debates that produce these advances. An unanticipated growth in the number of investigators requesting NP Core support, an emergent unforeseen condition limiting our core to create a digital library of glass slides, increasing request for postmortem CSF specimens and an unpredicted obsolescence of our essential equipment to be replaced, predicates this request.

We proposed in our recently funded P30 to provide open libraries of whole-slide scanned images to computer scientists and other investigators utilizing the scanners located in the department of pathology. However, due to increasing demand for neoplastic and other pathology specimens in the department, we have not been able to

use this service properly as the current scanner is slow and the department cannot allocate proper time needed for our “research” projects. On the other hand, we have started working with computer scientists in different centers to utilize artificial intelligence (AI)/machine learning to quantify pathologic findings such as amyloid

plaques and tangles in neurodegenerative diseases. However, the lack of access to a whole-slide scanner has incumbered our progress. Meanwhile, as the expectation was created, now we have increasing demand for a service we are unable to properly deliver and did not include its cost in submitted P30 budget. Secondly, we

realize a need to extend our effort to collect postmortem cerebrospinal fluid to address increasing demand for this valuable specimen and assist our biomarker core for their biomarker studies. Neuropathology Core activities continue to rapidly grow, requiring a more comprehensive formal database program to support a higher level of Core documentation and inventory performance. Finally, we underestimated

the rate of degeneration in our essential equipment such as tissue processor and microtome and their lack of extended technical support from their manufacturers for the coming years. For sustainable growth, we must replace them with a new reliable machine to be functional and supported for at least the next 10-years.