# Novel Approaches to Understand the Pathogenesis and Treat Alzheimer's Disease

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $2,484,793

## Abstract

OVERALL PROGRAM SUMMARY/ABSTRACT
In this P01 proposal entitled: “Novel Approaches to Understand the Pathogenesis and Treat Alzheimer’s
Disease”, we seek to gain a better understanding of the heterogeneous pathogenesis of AD and how it is
influenced by apolipoprotein (apo) E isotypes. The apoE4 allele is the major genetic risk factor for late-onset
AD and has been strongly associated with increased amyloid plaques deposition in brain parenchyma and
advanced vascular amyloid pathology; as well as, enhanced Aβ oligomerization. ApoE is also involved in
synaptic plasticity, glucose metabolism, mitochondrial function, and vascular integrity. Currently, there is no
consensus on how different apoE genotypes contribute to the pathogenesis of AD. The interrelated studies
proposed in the three projects of this P01 will help elucidate this complex role of apoE in AD. Hence this P01 is
addressing an issue of great significance. We propose an integrated, multidisciplinary research endeavor that
brings together investigators with an extensive history of successful collaboration, who have expertise in
diverse areas including proteomics, bioinformatics, neuropathology, AD mouse models, immunology, µMRI,
µPET, medicinal chemistry and biomarker studies. Across all projects we will apply our innovative proteomic
methods (with the assistance of the proteomics/neuropathology Core B) and use of common AD models and
behavioral assessments (with the assistance of the transgenic/behavioral Core C), along with state-of-the-art
biomarker technology using SIMOA and P01 investigator developed µMRI methodologies, to ensure synergism
across all P01 studies. Scientific rigor of the P01 will be ensure by the Biostatistics and Bioinformatics Core
(Core D). The three projects of this P01 are focused on the differential role apolipoprotein E (apoE) isoforms
play in: 1) AD plaque and vessel amyloid development as assessed by unbiased proteomics across the full
spectrum of AD pathology (Project 1); 2) innovative therapeutic approaches that target the Aβ/apoE interaction
(Project 2); and 3) responses to our novel therapeutic immunomodulation that targets abnormal conformation
(Project 3). Combined our efforts are anticipated to enhance our understanding of the differential effects of
apoE isotypes on AD pathogenesis and accelerate the discovery of effective therapeutic approaches that
address these diverse roles.

## Key facts

- **NIH application ID:** 9853940
- **Project number:** 1P01AG060882-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** THOMAS M WISNIEWSKI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,484,793
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853940

## Citation

> US National Institutes of Health, RePORTER application 9853940, Novel Approaches to Understand the Pathogenesis and Treat Alzheimer's Disease (1P01AG060882-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853940. Licensed CC0.

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