# Microbial Impact on NeuroDegeneration in Alzheimer's Dementia: MIND-AD

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $871,255

## Abstract

Alzheimer’s disease is a major threat to public health. Because Alzheimer’s disease has no cure, it is critical to
identify its modifiable risk factors that can be targeted to reduce its burden. Although initial evidence suggests
its plausibility, relatively little attention has been paid to the role of common infections in Alzheimer’s disease
etiology. We propose to investigate the association of infection with common pathogens—Herpes Simplex
Virus Types 1 and 2, Cytomegalovirus, Epstein-Barr Virus, Toxoplasma gondii—measured four times over ~25
years, and SARS-CoV-2 (the virus that causes COVID-19), with: (a) cognitive decline, and adjudicated mild
cognitive impairment (MCI) and dementia diagnoses; (b) plasma biomarkers of Alzheimer’s disease; and (c)
markers of physiological aging (telomere shortening, cyclin-dependent kinase inhibitor p16INK4a, plasma-derived
senescence-associated secretory phenotypes, and epigenetic clocks). We will also explore sex, Alzheimer’s
disease risk genes, and stress-related exposures (mental disorders and their symptoms, stressful life events,
and poor sleep) as moderators that amplify the risk of adverse infection-induced cognitive, brain health, and
physiological aging outcomes. Inclusion of viral specific CD8 T-cell differentiation in combination with antibody
levels measured serially in the same individuals will allow us to distinguish between long-term infections and
reactivation and to evaluate the influence of the course of both infection and immune response to infection, on
our outcomes. Senescence-associated secretory phenotypes will point to novel senescent pathways by which
infections affect brain health. We will accomplish this using existing data and collecting new data from
participants in the Baltimore Epidemiological Catchment Area (ECA) Study Follow-up, which has been
assessed five times for >35 years (mean age = 70 years, range 58-100). Blood specimens have been collected
three times over ~25 years in the ECA, and we will collect an additional blood draw to obtain infection status at
four time points, providing a rare opportunity to quantify timing of exposure and reactivation of latent infections
in relation to cognitive and functional decline and Alzheimer’s disease biomarkers and potential pathways. The
MPIs of the proposed study are currently completing Wave 5 of data collection in the ECA, including measures
of cognitive and functional decline, adjudicated MCI and dementia diagnoses, cellular aging and genome-wide
genetic and epigenetics assays. Our preliminary data in the ECA link common pathogens of interest with lower
cognitive performance and suggest effect modification by apolipoprotein E genotype. Our team consists of
experts in cognitive aging and Alzheimer’s disease, neurovirology, neuropsychology, Alzheimer’s disease
biomarkers, genetics and epigenetics, and the biology of aging. Results will clarify the extent to which
common infections increase the risk for Alzheimer’s disease and ...

## Key facts

- **NIH application ID:** 10491877
- **Project number:** 5R01AG075996-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Brion S Maher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $871,255
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491877

## Citation

> US National Institutes of Health, RePORTER application 10491877, Microbial Impact on NeuroDegeneration in Alzheimer's Dementia: MIND-AD (5R01AG075996-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10491877. Licensed CC0.

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