# The infectious etiology of Alzheimer's disease revealed at nanoscale precision

> **NIH NIH R56** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $1,543,629

## Abstract

The pathogen hypothesis of Alzheimer's disease (AD) proposes that viruses, bacteria, and other pathogens
play a role in the etiology of AD. Most studies that have looked for pathogens in the AD brain have used
sequencing, which detects nucleic acids but lacks the ability to pinpoint the location, morphology, and state of
pathogens, important for probing how pathogens might couple to specific AD hallmark molecular pathologies
(e.g., amyloid, hyperphosphorylated tau, and other hallmarks). Ideally one would be able to perform nanoscale
resolution, molecularly multiplexed, mapping of pathogens with respect to AD hallmark molecular pathologies.
We recently invented a new tool, expansion microscopy (ExM), which physically magnifies specimens so that
molecular information can be imaged in a molecularly multiplexed fashion, with nanoscale precision,
throughout intact tissues, on ordinary high-speed light microscopes. ExM is increasingly popular, with over
350 groups having undergone hands-on training on the procedure from us, and over 100 papers having
performed ExM. Accordingly, we will in this study use ExM to systematically study the location, morphology,
and state of the AD microbiome, thus yielding maps that can reveal how aspects of the AD microbiome relate
to molecular pathologies associated with AD. We have assembled a complementary team of a half-dozen
expert AD groups and technology-oriented groups, so that we can systematically probe this question from
multiple angles. Specifically we will derive (Aim 1) a subcellular-resolution map of the AD microbiome in
human brain specimens. We will then perform a (Aim 2) comparison of AD microbiomes to the temporal
progression of AD molecular pathologies. Finally, we will examine the (Aim 3) spatial transcriptomics of
microglia in relation to pathogens. Our hope is to reveal the fundamental organization of the AD microbiome
and multiple AD hallmark molecular pathologies, so that it is possible to systematically generate specific
hypotheses about mechanisms of, and targets for treating, AD.

## Key facts

- **NIH application ID:** 10236624
- **Project number:** 1R56AG069192-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Bobae An
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,543,629
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236624

## Citation

> US National Institutes of Health, RePORTER application 10236624, The infectious etiology of Alzheimer's disease revealed at nanoscale precision (1R56AG069192-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10236624. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*