# Role of Fibrinogen in Alzheimer's Disease

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2024 · $773,722

## Abstract

PROJECT SUMMARY
Alzheimer's disease (AD) is a multifactorial disorder with many pathogenic elements. One contributing factor is
vascular dysfunction, which can be both a result of the primary AD pathogenesis and a cause of neuronal loss
and subsequent cognitive impairment. The molecular mechanisms by which AD and the vascular system
intersect and influence each other are still unclear. We have been working for two decades to try to better
define this molecular interaction.
We have shown that beta amyloid (Aβ), the peptide that is a driver of AD, interacts with fibrinogen and
increases blood clot formation. These clots have an altered structure and are resistant to lysis. These
abnormal clots can contribute to reduced blood flow and increased inflammation, both of which could
contribute to vascular contributions to AD.
We have now found that the Aβ/fibrinogen complexes can have toxic effects independent of clotting. In
hippocampal slice cultures, Aβ/fibrinogen complexes are more toxic than either Aβ or fibrinogen alone. These
results identify a new mechanism by which the interaction of Aβ and fibrinogen can lead to neuronal
dysfunction.
Mutant and longer forms of Aβ are sometimes much more toxic that the classical Aβ42 and Aβ40 species. We
show that some mutant forms of Aβ that are more toxic interact much more strongly with fibrinogen. These Aβ
variants provide an entrée for studying the mechanisms by which Aβ/fibrinogen complexes are toxic in AD.
Therefore, our main goal is to explore the cellular and molecular mechanisms by which Aβ variants and their
fibrinogen complexes negatively affect the brain.

## Key facts

- **NIH application ID:** 10896372
- **Project number:** 5R01NS106668-07
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Erin H. Norris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $773,722
- **Award type:** 5
- **Project period:** 2018-04-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896372

## Citation

> US National Institutes of Health, RePORTER application 10896372, Role of Fibrinogen in Alzheimer's Disease (5R01NS106668-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10896372. Licensed CC0.

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