# IGF-1 and Alzheimer's Disease

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $380,000

## Abstract

SUMMARY
Alzheimer's disease and related dementias are a major public health problem in the United States and
worldwide. Although the etiology is not completely understood most patients with Alzheimer's disease have
evidence of vascular pathology, thus there is increasing interest in understanding the vascular contribution
to cognitive impairment and Alzheimer's disease. There is a major overlap between the risk factors for
vascular disease and those for Alzheimer's, including for instance, type II diabetes and insulin resistance,
hypertension, hypercholesterolemia, overweight and smoking. These risk factors are major causes of
intracranial vascular disease including atherosclerosis, arteriolosclerosis and cerebral amyloid angiopathy
leading to infarcts and microinfarcts. Insulin like growth factor-1 (IGF-1) is an endocrine and
autocrine/paracrine growth factor that has pleiotropic effects on metabolism, growth, differentiation and
survival. IGF-I and its receptor are expressed in the vasculature and we have shown that IGF-I administration
to hypercholesterolemic apoe-/-mice reduced vascular and systemic inflammation, oxidative stress, smooth
muscle cell apoptosis and atherosclerosis. We are now testing the anti-atherogenic effects of IGF-I in familial
hypercholesterolemic Rapacz pigs, a large animal model that has major advantages over rodent models
because of its anatomy and physiology being much more similar to humans. IGF-I is also produced within
the central nervous system, crosses the blood brain barrier and has pleiotropic neuroprotective effects.
However there is significant controversy regarding the potential role of IGF-I in Alzheimer's disease. While
observational studies and some rodent studies have suggested that IGF may have beneficial effects on beta-
amyloid accumulation and on the risk for Alzheimer's disease, others have shown contradictory results.
Evidence suggests that reduced insulin and IGF-I signaling may play a role in the development of Alzheimer's
disease. As with cardiovascular disease, small animal models do not reproduce many features of human
neurodegenerative diseases. Neuroanatomical studies of the pig brain have shown a much stronger
resemblance between pigs and humans than between rodents and humans. We thus have a unique
opportunity to study the effect of IGF-I on intracranial vascular and brain disease including large vessel
atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy, infarcts and microinfarcts in a novel swine
model that develops advanced vascular disease. Correlations will be established between the degree of
vascular disease and the hallmarks of Alzheimer's disease, notably, beta-amyloid deposits and neurofibrillary
tangles, and exploratory transcriptomic, metabolomic and proteomic analysis of vascular and brain tissues
will be performed. The study should provide key insights into the development of cerebrovascular,
neurovascular and Alzheimer's disease and lay the groundwork for additi...

## Key facts

- **NIH application ID:** 10120476
- **Project number:** 3R01HL070241-16S1
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** PATRICE DELAFONTAINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,000
- **Award type:** 3
- **Project period:** 2002-12-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120476

## Citation

> US National Institutes of Health, RePORTER application 10120476, IGF-1 and Alzheimer's Disease (3R01HL070241-16S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10120476. Licensed CC0.

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