# Role of fibrinogen in Alzheimer's disease

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $544,139

## Abstract

PROJECT SUMMARY
Fibrin is the major protein component of blood clots and is critical for normal hemostasis. It is also well-
established that in addition to its beneficial function, excessive or persistent fibrin can lead to or exacerbate
many pathological conditions, including atherosclerosis, rheumatoid arthritis, stroke, spinal cord injury, multiple
sclerosis, muscular dystrophy, peripheral nerve regeneration, and even bacterial infection. Beta-amyloid (Aβ),
a peptide that contributes to Alzheimer’s disease (AD), binds to fibrinogen with high affinity. As a result of this
interaction, Aβ-induced fibrin clots have an abnormal structure and resist degradation. Persistent fibrin in the
brain’s blood vessels and/or the parenchyma would be deleterious to neuronal function. We therefore propose
to investigate how fibrin affects the pathogenesis of AD.
We have found that reducing fibrinogen levels in AD mouse models results in reduced pathology and better
cognitive ability. However, the mechanism by which fibrin accelerates neuronal degeneration remains
unknown. Two likely possibilities exist: 1) Occlusion – fibrin clots are deposited in the vascular and perivascular
space, resulting in reduced blood flow, increased Aβ accumulation, and neuronal damage due to deprivation of
oxygen and nutrients; and 2) Inflammation – fibrin deposits drive a chronic inflammatory state that leads to
cellular damage.
The central hypothesis of this application is that the persistent, structurally abnormal fibrin clots formed in the
presence of Aβ contribute to the inflammation and neurodegeneration observed in AD. We will examine the
effects of fibrin on AD pathogenesis in AD patients and mice using ex vivo clotting assays, genetics/imaging in
a mouse model, and biochemical analysis of human samples. These studies may provide insights for new
diagnostics and therapies for AD patients.

## Key facts

- **NIH application ID:** 9842016
- **Project number:** 5R01NS106668-03
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Erin H. Norris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $544,139
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842016

## Citation

> US National Institutes of Health, RePORTER application 9842016, Role of fibrinogen in Alzheimer's disease (5R01NS106668-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842016. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*