# Cross sensitization of diet and alcohol on binge behaviors and metabolic dysfunction

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2022 · $417,442

## Abstract

Summary
Cerebrovascular dysfunction is tightly linked to the deposition of amyloid plaques and neurofibrillary tangles in
the brain; hallmarks of Alzheimer’s disease (AD). High fat diets (HFD) and chronic over-consumption of alcohol
independently result in aberrant lipid metabolism which underlies the vascular dysfunction associated with
obesity, type II diabetes, vascular dementia, and AD. While HFD and alcohol are both linked to the development
of AD, there is limited information on how binge co-consumption of HFD and alcohol impact AD progression and
associated cognitive decline. Our parent R01 utilizes a novel behavioral mouse model of binge co-consumption
of HFD and alcohol which recapitulates clinical findings showing HFD increases alcohol intake and vice versa,
providing a unique behavioral model to dissect the pathways that go awry with over-consumption of HFD and
alcohol and how they impact the development of AD. HFD and chronic alcohol consumption have a profound
impact on the speciation, composition, and function of plasma lipoproteins which modulate multiple metabolic
pathways including systemic immune response, inflammation, glucose metabolism and oxidative stress.
Lipoprotein function are mostly dominated by a handful of dynamic “scaffold” proteins that reside at the water-
lipid interface, in particular apolipoprotein E (APOE) which has three isoforms—APOE2, APOE3, and APOE4.
APOE4 is associated with elevated neuroinflammation and lower rates of cerebral glucose metabolism and
carriers of APOE4 are at substantially elevated risk for early onset and increased severity of AD. We hypothesize
that HFD and chronic alcohol consumption alter the speciation and compositional signatures of APOE-containing
lipoproteins which exacerbates the neuroimmune response and accelerates cognitive decline and development
of AD. Our specific aim is to characterize the impact of binge co-consumption of HFD and alcohol on the
speciation and composition of APOE3 and APOE4-containing lipoproteins and how they modulate the
development of AD. Utilizing transgenic mouse lines susceptible to Alzheimer’s Disease phenotypes with
humanize APOE isoforms, we will determine how co-morbid high fat diet and alcohol binge consumption
modulates memory function, insulin and glucose function, hippocampal neuroinflammation, and plasma
lipoprotein speciation.

## Key facts

- **NIH application ID:** 10501123
- **Project number:** 3R01AA026865-04S1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Yuval Silberman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $417,442
- **Award type:** 3
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501123

## Citation

> US National Institutes of Health, RePORTER application 10501123, Cross sensitization of diet and alcohol on binge behaviors and metabolic dysfunction (3R01AA026865-04S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10501123. Licensed CC0.

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