# Adult Changes in Thought (ACT) Research Program Core D: Neuropathology Core

> **NIH NIH U19** · KAISER FOUNDATION RESEARCH INSTITUTE · 2021 · $1,310,728

## Abstract

SUMMARY
The Adult Changes in Thought (ACT) Neuropathology (NP) Core (Core D) has been a valuable and frequently
utilized resource for the ACT cohort and supports the ACT Repository where the most generous gift to science
– a person’s brain – is used to maximize impact on local and national science of Alzheimer’s disease and
related dementias (ADRD). The NP Core has instituted rapid protocols designed for cutting edge molecular cell
profiling and has markedly extended sampling strategies to better capture regional changes that underlie the
heterogeneity of Alzheimer’s disease and related dementias. The NP Core has fostered development of
innovative, highly quantitative approaches to assess the neuropathology of ADRD, building on this important
tradition by integrating imaging technologies and analytical approaches to target and quantify gross and
microscopic pathology. We perform post-mortem MRI on every brain, generate 3D virtual brain reconstructions
leveraging unique brain sectioning techniques in the NP Core, scan slides of prospective and archival ACT
samples for traditional quantitative image analysis supplemented with deep learning approaches to maximize
information yield, and leverage multiplexed solution-phase assays from fixed-tissue protein extracts to
compare cytoarchitectural and biochemical pathologic changes in ADRD. All of these innovations are designed
to enable us to deeply characterize the structural substrate for ADRD heterogeneity, mechanisms of resilience
and resistance, and the biological basis of cognitive subtypes and functional variations in brain aging and
dementia in support of each of the ACT Cores. We combine this comprehensive analysis of human brains with
a leptomeningeal cell resource and neuropathological characterization for mechanistic explorations of AD
pathophysiology (Project 3) and promote existing collaborations focused on characterizing cell type
vulnerabilities in all stages of AD to inform mechanistic, diagnostic, and therapeutic research. The NP Core
interacts with and supports every other ACT U19 Research Program Core and Project through state-of-the-art
diagnostics and has expanded dissection and assessment protocols specifically tailored to support Project 2.
Thus, our Aims reflect our commitment to integrate traditional diagnostic excellence and extensive tissue and
data sharing with radiographically informed extensive sampling and a battery of highly quantitative, molecularly
specific tissue and in silico approaches to precisely measure ADRD neuropathology. Our specific Aims are to
(1) build a highly accessible repository of brain tissue and fluids, (2) provide diagnostic expertise according to
the latest guidelines, (3) develop innovative approaches, and (4) promote durable ADRD research through
support of ACT Cores and Projects. All of our research activities are focused on enhancing the research value
of tissue and body fluid donations from cognitively healthy ACT participants and those along th...

## Key facts

- **NIH application ID:** 10168313
- **Project number:** 1U19AG066567-01A1
- **Recipient organization:** KAISER FOUNDATION RESEARCH INSTITUTE
- **Principal Investigator:** CHRISTOPHER DIRK KEENE
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,310,728
- **Award type:** 1
- **Project period:** 2021-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168313

## Citation

> US National Institutes of Health, RePORTER application 10168313, Adult Changes in Thought (ACT) Research Program Core D: Neuropathology Core (1U19AG066567-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168313. Licensed CC0.

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