# Role of the Contact System in Alzheimer's Disease

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $546,298

## Abstract

PROJECT SUMMARY
In addition to neuronal degeneration, many Alzheimer’s disease (AD) patients suffer from vascular
abnormalities and inflammation. The contact activation system may contribute to both of these pathologies
since it can launch both pro-thrombotic and pro-inflammatory pathways. We have shown that the contact
system is significantly more activated in AD patients and AD mouse models compared to control groups. The
beta-amyloid peptide (Aβ), a driver of AD pathology, can activate Factor 12 (F12), the initiator of the contact
system. We have recently shown that depletion of F12 ameliorates pathology in AD mice at early stages of
disease. These results indicate that excess contact system activation may promote AD pathology and cognitive
decline.
There is no effective treatment for AD. A link between F12 activation and the pathogenesis of AD provides a
possible novel approach to treatment. The contact system is an attractive target for AD therapy; humans
deficient in F12 and mice with knockout of different contact system pathway genes have normal hemostasis. If
F12 activation is indeed deleterious in AD pathology, therapies designed to block the contact system might
slow disease progression while not affecting normal hemostasis. Thus, our studies may reveal new targets to
suppress both thrombotic and inflammatory contributions to AD progression. Positive results might be able to
be applied to AD patients rapidly as already FDA-approved drugs targeting the contact system already exist.

## Key facts

- **NIH application ID:** 10112965
- **Project number:** 5R01NS102721-04
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Erin H. Norris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $546,298
- **Award type:** 5
- **Project period:** 2018-04-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112965

## Citation

> US National Institutes of Health, RePORTER application 10112965, Role of the Contact System in Alzheimer's Disease (5R01NS102721-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112965. Licensed CC0.

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