Glycolysis-enhancing α 1 -adrenergic antagonists have therapeutic potential in Alzheimer's disease

Qiang Zhang; Jordan L Schultz; Jacob E Simmering; Braedon Q Kirkpatrick; Matthew A Weber; Sydney Skuodas; Tara Hicks; Grace Pierce; Margaret Laughlin; Benu George; Aimee X Bertolli; Travis Larson; Ramasamy Thangavel; Mayu Oya; David K Meyerholz; Georgina Aldridge; Jan Fassler; Nandakumar S Narayanan

doi:10.1186/s13195-026-02135-z

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Glycolysis-enhancing α 1 -adrenergic antagonists have therapeutic potential in Alzheimer's disease

Journal article

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Glycolysis-enhancing α 1 -adrenergic antagonists have therapeutic potential in Alzheimer's disease

Qiang Zhang, Jordan L Schultz, Jacob E Simmering, Braedon Q Kirkpatrick, Matthew A Weber, Sydney Skuodas, Tara Hicks, Grace Pierce, Margaret Laughlin, Benu George, …

Alzheimer's research & therapy

07/09/2026

DOI: 10.1186/s13195-026-02135-z

PMID: 42426853

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Abstract

Terazosin (TZ) is widely prescribed for hypertension and benign prostatic hyperplasia. Recent studies suggest that TZ enhances glycolysis and may protect against neurodegenerative diseases. We tested the hypothesis that TZ is neuroprotective in Alzheimer's disease (AD) in a yeast model, a mouse model, and two human datasets. 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. These data provide preliminary evidence that glycolysis-enhancing drugs have therapeutic potential in AD.

Details

Title: Subtitle: Glycolysis-enhancing α 1 -adrenergic antagonists have therapeutic potential in Alzheimer's disease
Creators: Qiang Zhang - University of Iowa
Jordan L Schultz - University of Iowa
Jacob E Simmering - University of Iowa
Braedon Q Kirkpatrick - University of Iowa
Matthew A Weber - University of Iowa
Sydney Skuodas - University of Iowa
Tara Hicks - University of Iowa
Grace Pierce - University of Iowa
Margaret Laughlin - University of Iowa
Benu George - University of Iowa, Neurology
Aimee X Bertolli - University of Iowa
Travis Larson - Duke University
Ramasamy Thangavel - University of Iowa
Mayu Oya - Johns Hopkins University
David K Meyerholz - University of Iowa
Georgina Aldridge - University of Iowa
Jan Fassler - University of Iowa
Nandakumar S Narayanan - University of Iowa
Resource Type: Journal article
Publication Details: Alzheimer's research & therapy
DOI: 10.1186/s13195-026-02135-z
PMID: 42426853
eISSN: 1758-9193
Publisher: Springer Nature
Grant note: R01 NS120987 / NIH HHS R01 NS129711 / NIH HHS Cannon-Williams Faculty Fellowship / University of Iowa R03 AG078787 / NIH HHS
Language: English
Electronic publication date: 07/09/2026
Academic Unit: Neurology; Pulmonary, Critical Care, and Occupational Medicine; Psychiatry; Health Management and Policy; Pathology; Iowa Neuroscience Institute; Biology; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9985180978402771

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