# Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis

> **NIH ALLCDC R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2022 · $499,719

## Abstract

Project Summary/Abstract
 We propose to study the relation between blood concentrations of persistent organic pollutants (POPs)
and amyotrophic lateral sclerosis (ALS) incidence and survival using blood samples collected well before the
onset of ALS. We will also explore whether those exposures, and ALS, are associated with changes in
extracellular vesicles (EV) derived specifically from immune system cells to identify mechanisms related to the
exposures, ALS, and associations between them. We will conduct a case-control study nested within large
prospective cohort studies in Denmark and Finland that total almost 120,000 participants. The participants
provided blood samples at the cohort baselines, and we identify ALS cases during follow-up via linkage with
National registries. We anticipate a total of 265 ALS cases that occurred after cohort enrollment. We will
randomly select 2 controls per case individually matched on age, sex, and cohort from among all non-ALS
cases alive at the time the case is diagnosed. Extensive questionnaire data from the cohorts is available for
regression model adjustments. The blood samples will be analyzed for organochlorine pesticides,
polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). EVs will be isolated and
characterized in terms of size and number, and percentage expressing specific surface markers that identify
EVs derived from cells of the immune system. By nesting this study within large Danish and Finnish
prospective cohort studies that have blood samples from many years before ALS, we have a unique setting
that will allow us for the first time to assess the relation between toxicant exposures and ALS using individual
biomarkers of exposure from samples collected before ALS onset, thereby avoiding problems associated with
questionnaire recall of past exposures or biomarker measurements in samples collected after ALS onset that
may be affected by disease (leading to possible reverse causation). The pre-disease biosamples also allow us
to explore biological mechanisms that may underlie the associations we see and possibly identify biomarkers
of future disease risk and survival, thereby providing insight into ALS pathophysiology.

## Key facts

- **NIH application ID:** 10438145
- **Project number:** 5R01TS000315-03
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Marc G Weisskopf
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2022
- **Award amount:** $499,719
- **Award type:** 5
- **Project period:** 2020-09-30 → 2023-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438145

## Citation

> US National Institutes of Health, RePORTER application 10438145, Pre-disease biomarkers of persistent organic pollutants, immune system, and amyotrophic lateral sclerosis (5R01TS000315-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10438145. Licensed CC0.

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