Investigating the role of long-term latent herpes simplex virus infection on APOE4-associated alzheimer's disease pathogenesis
Active Project Grant Awarded Last action
- Award ID
- R01AG083963
- Recipient
-
The Trustees Of Columbia University In The City Of New York UEI QHF5ZZ114M72
- Awarding agency
-
National Institute on Aging
National Institutes of Health, Department of Health and Human Services
- Obligated
- $4,112,823
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date 69% complete
- Place of performance
- New York, NY 10032, USA
Award details come from USAspending.gov.
Description
- Abstract
- 47 million people worldwide are living with alzheimer's disease (ad) or a related form of dementia. In the US alone, the annual health care costs for people with ad will exceed 1 trillion dollars by 2050. However, current treatments do not robustly prevent disease progression. The major risk factors for the late-onset form of ad are advanced age and possession of the E4 allele of apolipoprotein E (APOE). Importantly, increasing data support the hypothesis that latent herpes simplex virus 1 (HSV-1) infection is also a risk factor, especially in combination with the APOE4 allele. This suggests that current antivirals may halt or delay neurodegenerative disease progression in APOE4 carriers who are infected with HSV-1. A major GAP in the study of this association, however, is the absence of an HSV infection model reflecting the complexity of long-term latent infection, particularly in the context of APOE4 and ad. In our preliminary studies, we observed that HSV-1-infected APOE4 mice, compared to mock-infected APOE4 mice and HSV-1-infected WT mice, displayed robust spatial memory deficits, as well as oxidative stress, iron dysregulation, and gliosis in the CNS when assessed 15 months post infection (MPI), but not at 3 MPI. The objective of this proposal is to use this model, as well as complementary in vitro models, to fully elucidate the effects of long-term latent HSV-1 infection, in the context of differential APOE isoform expression, on brain function and ad pathogenesis. We will also assess whether treatment with a novel, brain-penetrant antiviral medication can block these effects. We anticipate that the full study proposed herein will uncover unique and important interactions between HSV-1 infection and APOE genotype in driving ad pathogenesis, potentially leading to safe and effective new therapeutic strategies for preventing or slowing ad in at-risk individuals.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $816,677 | |
| Amendment | $804,313 | |
| Amendment | $828,847 | |
| Amendment | $831,493 | |
| Original award | $831,493 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| The Mclaughlin Research Institute For Biomedical Sciences, Inc. | $186,991 | |
| Rector & Visitors Of The University Of Virginia | $271,029 | |
| Cincinnati Univ Of | $45,268 | |
| The Mclaughlin Research Institute For Biomedical Sciences, Inc. | $278,730 | |
| Rector & Visitors Of The University Of Virginia | $278,730 | |
| The Mclaughlin Research Institute For Biomedical Sciences, Inc. | $186,991 | |
| Cincinnati Univ Of | $22,612 | |
| The Mclaughlin Research Institute For Biomedical Sciences, Inc. | $186,991 |
Quick answers
Who received award R01AG083963?
R01AG083963 was awarded to The Trustees Of Columbia University In The City Of New York by National Institute on Aging (National Institutes of Health) on August 15, 2023.
How much is award R01AG083963 worth?
$4,112,823 has been obligated on R01AG083963.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award