# Complex odor recognition of the main olfactory bulb

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $387,386

## Abstract

PROJECT SUMMARY
Alzheimer's disease is characterized by accumulation of insoluble forms of amyloid-β (Aβ) in the extracellular
space and within vessel walls, aggregation of the microtubule protein tau in intracellular neurofibrillary tangles
and neuroinflammation - contributing to neuronal damage and clinical dementia. A critical barrier in treating
Alzheimer's disease is the years to decades-long lag between initiation of disease and clinical diagnosis, when
reversal of brain pathology and recovery of neurons may at best, slow cognitive decline. Thus, it is essential to
identify the pathological processes in early disease to characterize biomarkers for diagnosis and find
interventional targets that will halt disease prior to symptoms and signs of dementia. An early phenotype of
Alzheimer's is olfactory dysfunction. Using a novel, targeted RNA sequencing strategy (BioSpyder TempO-
Seq), we found that compared to controls, viral/amyloid processing pathways are activated in OBs and
olfactory tracts dissected from formalin-fixed, paraffin-embedded (FFPE) tissue of individuals with familial and
sporadic Alzheimer's disease (FAD and SAD). The discovery of viral infection in the OB and OT in Alzheimer's
opens a potentially exciting, new avenue of research that links 2 disparate, underexplored areas of
Alzheimer's disease pathogenesis: (1) olfactory dysfunction in early Alzheimer's disease that is
characterized by the loss of sense of smell, by Aβ deposition in the glomeruli of the OB, and by stage-
dependent deregulation of specific pathways including neuroinflammation in olfactory bulb, and; (2) the
association of herpesviruses with Alzheimer's disease, including the increased frequency of herpes
simpex virus type 1 (HSV-1) in brains from Alzheimer's disease patients and HSV-1-induced acceleration of
amyloid deposition in mice and human neural cultures. Taken together, we hypothesize that productive
HSV-1 infection within the olfactory epithelium results in inflammatory activation of glomeruli in the OB
of AD patients, overall producing a neuroinflammatory environment that accelerates olfactory
dysfunction and progression of AD. To test this hypothesis, we will: Aim 1. Use intranasal inoculation with
HSV1 to study microglial responses and formation of amyloid in the OB, and olfactory dysfunction in 5xFAD
and controls, and; Aim 2. Compare the gene expression profiles of HSV-1-infected OB and OT from the 2
cohorts of animals described above with that of previously analyzed FAD and SAD OB and OT using the
BioSpyder TempO-Seq RNAseq assay. The experiments proposed here are within the scope of the
parent grant DC000566 that investigates through combined behavioral, two photon imaging and
electrophysiological recording olfactory function in mice and are significant since they will identify
pathogenic mechanisms that occur in early AD prior to the onset of clinical dementia that can provide
early biomarkers for diagnosis and therapeutic targets to slow or ha...

## Key facts

- **NIH application ID:** 10119714
- **Project number:** 3R01DC000566-31S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Diego Restrepo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,386
- **Award type:** 3
- **Project period:** 1988-12-12 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119714

## Citation

> US National Institutes of Health, RePORTER application 10119714, Complex odor recognition of the main olfactory bulb (3R01DC000566-31S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10119714. Licensed CC0.

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