ArticleBrain research2012
Evaluation of the effects of testosterone and luteinizing hormone on regulation of β-amyloid in male 3xTg-AD mice.
Article in Brain research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04335682 (A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide), which is not on this map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG)
Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Gonadotropins Across the Lifespan: Their role in the Neurodevelopment-Neurodegeneration Continuum.The Yale journal of biology and medicine · 2026Review
- Sex differences in the relationship between depression and Alzheimer's disease-mechanisms, genetics, and therapeutic opportunities.Frontiers in aging neuroscience · 2024Review
- Testosterone deficiency worsens mitochondrial dysfunction in APP/PS1 mice.Frontiers in aging neuroscience · 2024Article
- Exploring the Intricate Nexus of Sarcopenia and Cognitive Impairment.Aging and disease · 2023Review
- Sexual Dimorphism in Neurodegenerative Diseases and in Brain Ischemia.Biomolecules · 2022Review
- Testosterone, cognitive decline and dementia in ageing men.Reviews in endocrine & metabolic disorders · 2022Review
- High-fat diet exacerbates cognitive decline in mouse models of Alzheimer's disease and mixed dementia in a sex-dependent manner.Journal of neuroinflammation · 2022Article
- GnRH pulse frequency and irregularity play a role in male aging.Nature aging · 2021Article
- Biomarkers to Evaluate Androgen Deprivation Therapy for Prostate Cancer and Risk of Alzheimer's Disease and Neurodegeneration: Old Drugs, New Concerns.Frontiers in oncology · 2021Review
- Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research.Journal of Alzheimer's disease : JAD · 2021Review
- Steroids and Alzheimer's Disease: Changes Associated with Pathology and Therapeutic Potential.International journal of molecular sciences · 2020Review
- Chronological Molecular Changes in Neuronal Communication in Androgen-Deficient Rats.Journal of molecular neuroscience : MN · 2019Article
- On the central role of mitochondria dysfunction and oxidative stress in Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Review
- Article
- Supraphysiologic-dose anabolic-androgenic steroid use: A risk factor for dementia?Neuroscience and biobehavioral reviews · 2019Review
- Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer.Prostate cancer and prostatic diseases · 2018Article
- Androgen alleviates neurotoxicity of β-amyloid peptide (Aβ) by promoting microglial clearance of Aβ and inhibiting microglial inflammatory response to Aβ.CNS neuroscience & therapeutics · 2017Article
- The importance of studying sex differences in disease: The example of multiple sclerosis.Journal of neuroscience research · 2017Review
- LW-AFC, a new formula derived from Liuwei Dihuang decoction, ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in PrP-hAβPPswe/PS1Alzheimer's research & therapy · 2016Article
- The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.Hormones and behavior · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
During normal aging, men experience a significant decline in testosterone levels and a compensatory elevation in levels of gonadotropin luteinizing hormone (LH). Both low testosterone and elevated LH have been identified as significant risk factors for the development of Alzheimer's disease (AD) in men. It is unclear whether changes in testosterone or LH primarily underlie the relationship with AD, and therefore may be a more suitable therapeutic target. To examine this issue, we compared levels of β-amyloid (Aβ) immunoreactivity in male 3xTg-AD mice under varying experimental conditions associated with relatively low or high levels of testosterone and/or LH. In gonadally intact mice, Aβ accumulation increased after treatment with the gonadotropin-releasing hormone agonist leuprolide, which inhibits the hypothalamic-pituitary-gonadal (HPG) axis and reduces both testosterone and LH levels. In gonadectomized (GDX) mice with low testosterone and high LH, we also observed increased Aβ levels. Treatment of GDX mice with testosterone significantly reduced Aβ levels. In contrast, leuprolide did not significantly decrease Aβ levels and moreover, inhibited the Aβ-lowering effect of testosterone. Evaluation of hippocampal-dependent behavior revealed parallel findings, with performance in GDX mice improved by testosterone but not leuprolide. These data suggest that Aβ-lowering actions of testosterone are mediated directly by androgen pathways rather than indirectly via regulation of LH and the HPG axis. These findings support the clinical evaluation of androgen therapy in the prevention and perhaps treatment of AD in hypogonadal men.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.