Glycolysis-enhancing α1-adrenergic antagonists have therapeutic potential in Alzheimer’s disease
9 affiliations
- 1Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 169 Newton Road, Iowa City, IA, 52242, USA. [email protected]
- 2Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA
- 3Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA
- 4Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 169 Newton Road, Iowa City, IA, 52242, USA
- 5Department of Biology, University of Iowa, Iowa City, IA, 52242, USA
- 6Duke Medical Scientist Training Program, Department of Neurobiology, Duke University, Durham, NC, 27710, USA
- 7Johns Hopkins University, Baltimore, MD, 21205, USA
- 8Department of Pathology, University of Iowa, Iowa City, IA, 52242, USA
- 9Department of Neurology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 169 Newton Road, Iowa City, IA, 52242, USA. [email protected]
Abstract
Background Terazosin (TZ) is widely prescribed for hypertension and benign prostatic hyperplasia. Recent studies suggest that TZ enhances glycolysis and may protect against neurodegenerative diseases. Methods We tested the hypothesis that TZ is neuroprotective in Alzheimer’s disease (AD) in a yeast model, a mouse model, and two human datasets. Results We report four main results. First, TZ increased ATP levels in a Saccharomyces cerevisiae mutant with impaired metabolism, and reduced Amyloid-beta42 (Aβ42) aggregation. Second, in 5xFAD mice, TZ attenuated amyloid pathology and rescued cognitive impairments in spatial memory and interval timing. Third, in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, AD patients taking glycolysis-enhancing drugs had a slower progression of both cognitive dysfunction and metabolic neuroimaging biomarkers (18 F-fluorodeoxyglucose positron emission tomography (FDG-PET)). Finally, in the Merative Marketscan dataset, patients taking glycolysis-enhancing drugs had lower risks of developing AD. Conclusion These data provide preliminary evidence that glycolysis-enhancing drugs have therapeutic potential in AD.
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BibTeX
@article{zhang2026glycolysisenhancing,
title = {{Glycolysis-enhancing α1-adrenergic antagonists have therapeutic potential in Alzheimer’s disease}},
author = {Qiang Zhang and Jordan L. Schultz and Jacob E. Simmering and Braedon Q Kirkpatrick and Matthew A. Weber and Sydney Skuodas and Tara Hicks and Grace Pierce and Margaret Laughlin and Benu George and Aimee X. Bertolli and Travis Larson and Ramasamy Thangavel and Mayu Oya and David Kyle Meyerholz and Georgina M. Aldridge and Jan S. Fassler and Nandakumar Narayanan},
journal = {Alzheimer s Research \& Therapy},
year = {2026},
month = jul,
doi = {10.1186/s13195-026-02135-z},
url = {https://doi.org/10.1186/s13195-026-02135-z},
note = {CC BY},
}
RIS
TY - JOUR
TI - Glycolysis-enhancing α1-adrenergic antagonists have therapeutic potential in Alzheimer’s disease
AU - Qiang Zhang
AU - Jordan L. Schultz
AU - Jacob E. Simmering
AU - Braedon Q Kirkpatrick
AU - Matthew A. Weber
AU - Sydney Skuodas
AU - Tara Hicks
AU - Grace Pierce
AU - Margaret Laughlin
AU - Benu George
AU - Aimee X. Bertolli
AU - Travis Larson
AU - Ramasamy Thangavel
AU - Mayu Oya
AU - David Kyle Meyerholz
AU - Georgina M. Aldridge
AU - Jan S. Fassler
AU - Nandakumar Narayanan
PY - 2026
DA - 2026/07/09
JO - Alzheimer s Research & Therapy
DO - 10.1186/s13195-026-02135-z
UR - https://doi.org/10.1186/s13195-026-02135-z
AB - Background Terazosin (TZ) is widely prescribed for hypertension and benign prostatic hyperplasia. Recent studies suggest that TZ enhances glycolysis and may protect against neurodegenerative diseases. Methods We tested the hypothesis that TZ is neuroprotective in Alzheimer’s disease (AD) in a yeast model, a mouse model, and two human datasets. Results We report four main results. First, TZ increased ATP levels in a Saccharomyces cerevisiae mutant with impaired metabolism, and reduced Amyloid-beta42 (Aβ42) aggregation. Second, in 5xFAD mice, TZ attenuated amyloid pathology and rescued cognitive impairments in spatial memory and interval timing. Third, in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, AD patients taking glycolysis-enhancing drugs had a slower progression of both cognitive dysfunction and metabolic neuroimaging biomarkers (18 F-fluorodeoxyglucose positron emission tomography (FDG-PET)). Finally, in the Merative Marketscan dataset, patients taking glycolysis-enhancing drugs had lower risks of developing AD. Conclusion These data provide preliminary evidence that glycolysis-enhancing drugs have therapeutic potential in AD.
SN - 1758-9193
ER -