# WTC Airborne Particulate and Climate Change as Risk Factors of Late-Onset Alzheimer's  Disease

> **NIH ALLCDC U01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $349,999

## Abstract

PROJECT SUMMARY: In the subsequent years following the World Trade Center (WTC) attack on September
11th, 2001, a cluster of chronic health conditions emerged among first responders (FRs) who were present during
the aftermath of the attack. Many FRs were at Ground Zero for prolonged periods in the first week after the
disaster, repeatedly exposing them to high levels of dust composed of particles of varying sizes that contained
metals, polychlorinated biphenyls, polyaromatic hydrocarbons, among many known toxins. A growing body of
scientific literature indicates that FRs who were exposed to high levels of dust for prolonged periods may have
a greater incidence of mild cognitive impairment (MCI), as well as other neurological complications i.e. changes
in white matter connectivity, decreased hippocampal volume which may put them at a greater risk of developing
Alzheimer's disease (AD). Crucially, the risk relating to exposure was elevated in individuals carrying the AD
vulnerability gene (i.e., apolipoprotein-E4 [APOE4], TREM2). Carrying a single APOE4 allele increases the risk
for AD by approximately 4-fold, while double carriers have a 10-fold increased risk compared to the neutral
APOE3 isoform. Based on this consideration, we have established the Late onset of Alzheimer's disease
(LOAD)2 mouse model which carries a humanized ApoE knock-in mutation for the E4 isoform, a CRISPR/Cas9-
generated APP allele with a humanized Aß1-42 region and R47H point mutation in the TREM2 gene to study
the effects of WTC airborne PM and the role of age and genetic and environmental risk factors on LOAD.
Additionally, in new studies, we found that the combination of experimental “extreme weather conditions” by heat
stress (HS) in mice, primed by exposure to WTC airborne PM, exacerbates impairment in energy metabolism,
altered lipid metabolism, and inflammatory responses. Consistent with this hypothesis, our feasibility evidence
shows that the combination of environmental risk factors (such as HS) to a single WTC airborne PM exposure
may negatively influence several metabolic cascades associated with energy metabolism. Based on this, our
proposed study will define an age-dependent interaction regarding environmental “climate changes” (HS) to
WTC airborne PM exposure on the onset and progression of LOAD. The overarching goal of this proposal is to
examine the impact of WTC airborne PM on age x genetic interactions in response to exposure to WTC airborne
PM and/or extreme weather conditions (HS), ultimately providing new strategies for risk assessment, risk
reduction, and disease prevention in LOAD. The choice to study the role of WTC airborne PM in LOAD2 mice is
fundamental to our understanding of age x genetic interactions in response to exposure to environmental
stressors. The proposed studies seek to explicitly test the hypothesis that exposure to toxic WTC airborne PM
causes long-term cognitive impairment and AD-type pathology by using rodent models. We understa...

## Key facts

- **NIH application ID:** 10995009
- **Project number:** 1U01OH012779-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Giulio Maria Pasinetti
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2024
- **Award amount:** $349,999
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995009

## Citation

> US National Institutes of Health, RePORTER application 10995009, WTC Airborne Particulate and Climate Change as Risk Factors of Late-Onset Alzheimer's  Disease (1U01OH012779-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10995009. Licensed CC0.

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