# Brain Effects of Lifetime Racial/Ethnic Discrimination on the LC-NE Function and the Risk for Alzheimer's Disease

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $836,123

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is a global crisis facing the aging population and society as a whole. Despite studies
suggesting that blacks may be at greater risk of developing AD, with 2-3 times higher prevalence rate of cognitive
impairment than whites, there have been few studies investigating health disparities, and blacks have been
underrepresented in many prominent U.S. AD biomarker studies and clinical trials. The current biomarker
classification system (i.e., the ATN model) does not fully account for health disparities and can’t explain the
increased prevalence among blacks of both AD and vascular risk factors for AD such as diabetes and
hypertension when compared to whites. Research on cognitive aging has traditionally focused on how decline
in various cortical and hippocampal regions influences cognition. However, tau pathology emerges decades
before amyloid pathology, appearing first in the brainstem; particularly in the locus coeruleus (LC), the source of
brain’s norepinephrine (NE). Our decade-long studies in humans using a norepinephrine transporter (NET)-
selective radiotracer ([11C]MRB) have demonstrated a special vulnerability of LC to aging and stress. Our
preliminary data reveals that the decline rate of NET, normally associated with aging due to loss in NET
availability and cell death, is much faster among blacks starting in the mid-30s, particularly in black males (e.g.,
2-3%/yr vs. 0.14-0.23%/yr in thalamus and brainstem for black males vs. white males (p<0.00001)). As the LC
plays a central role in the integration and orchestration of the adaptive CNS response to various stressors or
challenges, we hypothesize that
cumulative exposure to socioeconomic disadvantage and racial discrimination
may cause long-lasting changes in LC function followed by LC neuronal loss, which would explain the different
AD phenotypical clinical presentation among blacks (i.e., less tau burden but more LC loss and vascular
damage). Our hypothesis is also supported by the broad evidence that the LC is an early site of AD
neurodegeneration and LC cell density is more strongly associated with cognitive decline than other nuclei. We
propose to test this hypothesis by demonstrating that there will be age and race/ethnic differences on NET
availability (measured with [11C]MRB) across midlife and late-life in the LC and its target brain regions (Aim 1),
and that decreased NET availability is associated with stress levels and impaired cognition (Aim 2), as well as
the predictive value of NET availability on longitudinal change in cognition (Aim 3). There is the potential to
determine if dysfunction of the LC is: i) a potential marker for the increased AD pathology that is observed in
normal aging; ii) a key contributor to the development of metabolic syndrome, vascular dysfunction, and cognitive
decline, as result of chronic stress; iii) associated with increased prevalence of both AD and vascular risk factors
for AD in blacks when compared to ...

## Key facts

- **NIH application ID:** 10480028
- **Project number:** 5R01AG072644-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** YU-SHIN DING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $836,123
- **Award type:** 5
- **Project period:** 2021-09-05 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480028

## Citation

> US National Institutes of Health, RePORTER application 10480028, Brain Effects of Lifetime Racial/Ethnic Discrimination on the LC-NE Function and the Risk for Alzheimer's Disease (5R01AG072644-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10480028. Licensed CC0.

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