# Contribution of the Virome to Alzheimer's pathogenesis

> **NIH NIH DP1** · NORTHWESTERN UNIVERSITY · 2021 · $327,396

## Abstract

Alzheimer’s disease (AD) is a widespread age-related dementia of unknown etiology characterized by
neuronal loss, atrophy, and aggregation of beta amyloid (neuritic plaques) and microtubule associated tau
proteins (neurofibrillary tangles) in the brain. The major gap in our knowledge is what triggers AD
pathogenesis. While deposition of these proteins are thought to play an important role in the pathogenesis of
AD, the presence of these aggregates is not sufficient to cause AD. Both humans and experimental animal
models can exhibit one or both of these neuropathological changes without cognitive impairment. Thus, there
has been increasing effort to identify other risk factors, including infectious agents, that together with protein
aggregation could fully explain the etiology of this multifactorial disease. In particular, there is evidence that
infection by viral pathogens such as members of the Herpesviridae family of viruses could be risk factors for
developing AD. However, like protein aggregates, these viruses are also found in a significant number of healthy
individuals and are not consistently enriched in the brains of AD patients. Adequately powered and unbiased
studies testing for viral genetic material in AD patients and carefully selected control subjects are needed to
establish viral infection as a genuine risk factor. In addition, mechanistic experiments investigating the role of
these agents in the pathogenesis of AD are needed in order to reconcile infectious etiologies with more
established risk factors such as aging and pathological protein aggregation.
 As part of the parent DP1 grant, we have developed an unbiased target-enrichment deep-sequencing
platform, ViroFind, for identifying all viruses known to infect humans in clinical tissue samples, including post
mortem brains- the entire Virome. Our preliminary data indicate that adeno-associated virus (AAV) is enriched
in the cerebral cortex of AD patients.
Our long term goals are to decipher the pathogenesis of AD. Our overall objectives are to characterize the
entire virome in the brain of AD patients using ViroFind. Our central hypothesis is that known viruses, viruses
variants, or yet unknown viruses, are able to reach the CNS and remain latent by hiding into neurons, thereby
escaping detection from the immune system. Recurrent reactivations during aging triggers an immune and
inflammatory reaction with production of Aβ, which leads over the years to AD in certain individuals with genetic
predisposition. The rationale is that these proposed pilot studies will enable us to develop an initial
understanding of all the viral strains present in AD brains, as well as their cellular localization and whether they
are latent or replicating.To verify this hypothesis, we will carry out the following Specific Aim:
Aim 1. Determine whether viral infection correlates with the loss of adult neurogenesis in the human
hippocampus and whether these factors are associated with the development of...

## Key facts

- **NIH application ID:** 10287010
- **Project number:** 3DP1DA048493-04S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Igor J. Koralnik
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,396
- **Award type:** 3
- **Project period:** 2020-02-14 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287010

## Citation

> US National Institutes of Health, RePORTER application 10287010, Contribution of the Virome to Alzheimer's pathogenesis (3DP1DA048493-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10287010. Licensed CC0.

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