# BLR&D Research Career Scientist Award Application

> **NIH VA IK6** · JAMES J PETERS VA  MEDICAL CENTER · 2021 · —

## Abstract

SUMMARY
The goals of Dr. Pasinetti’s research is to investigate the biological processes that occur during aging when
subjects with normal cognitive function convert into the very earliest stages of Alzheimer’s disease (AD) and
then to frank dementia. Dr. Pasinetti has published his pivotal work in 356 manuscripts in journals including
Journal of Biochemistry, Nature, Neuron, and Cell. Dr. Pasinetti’s publications have an H impact factor of 64
and are cited 12,000 times according to Google Scholar. A brief synopsis of his research is provided below:
1) Alzheimer’s disease (AD) and type 2 diabetes (T2D) Dr. Pasinetti identified T2D as one of the major risk
factors that might affect AD neuropathology and synaptic plasticity in part through epigenetic mechanisms. In a
recent genome wide association study, we found a subpopulation of individuals with T2D have a genetic
predisposition to AD based on the evidence of shared common T2D/AD single nucleotide polymorphisms in
gene pathways involved in chromatin modification enzymes, among others. These studies will provide the
basis for novel therapeutic targets towards the preservation of cognitive health in a subset of T2D subjects at
risk for developing AD.
2) Drug discover and repurposing. Neurotoxic oligomeric β-amyloid (Aβ) peptides and misfolded tau have
been implicated in disruption of synaptic plasticity, contributing in part to mechanisms underlying onset and
progression of cognitive deterioration and eventually AD dementia. Using a structure-activity relationship (SAR)
approach, Dr. Pasinetti’s laboratory is “reconstructing” novel antihypertensive drugs lacking cardiovascular side
effects but with enhanced anti-Aβ oligomerization activity. Repurposing drugs has several advantages over
novel drugs since they are already well-characterized in respect to tolerability and safety profile.
3) Biomarkers of mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). Dr.
Pasinetti identified biomarkers to help diagnose two of the major “signature injuries” of the recent wars in Iraq
and Afghanistan: mTBI and PTSD. Dr. Pasinetti’s lab reported differential expression of four non-coding micro
RNAs in Veterans able to distinguish subjects with PTSD but not TBI. Such biomarkers could provide novel
benchmarks in patient selection with comorbid TBI/PTSD who are also at high risk for AD.
4) Molecular Integrative Neuroresilience. Dr. Pasinetti was awarded a P50 Research Center Grant on
“Molecular Integrative Neuroresilience” with the primary goal of understanding the mechanisms through which
recently identified polyphenolic compounds may promote resilience against stress-induced psychological and
cognitive impairment. Most importantly, the lab is currently leveraging the Research Center Activities in
mechanistic investigations related to safety and efficacy studies aimed at preventative and therapeutic
approaches to promote cognitive and psychological resilience in Gulf War Illness Veterans wit...

## Key facts

- **NIH application ID:** 10265349
- **Project number:** 5IK6BX003785-05
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** Giulio Maria Pasinetti
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265349

## Citation

> US National Institutes of Health, RePORTER application 10265349, BLR&D Research Career Scientist Award Application (5IK6BX003785-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10265349. Licensed CC0.

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