Long-term systemic androgen deprivation partially modulates neuroinflammation in male App mice.

Apr 28, 2025

Experts: Kasumi Maekawa,Akira Sobue,Okiru Komine,Yuko Saito,Shigeo Murayama,Takaomi C Saido,Takashi Saito,Koji Yamanaka

Alzheimer’s disease (AD) is the leading neurodegenerative disease manifesting cognitive impairment. Its procession is regulated by activated glial cell-mediated neuroinflammation. Although estrogen deprivation is a known risk factor for AD in females, the impact of androgen deprivation on AD pathology in males, particularly regarding neuroinflammation, remains unclear. This study investigates the effects of long-term systemic androgen deprivation on AD pathology, including glial cell-specific gene expression, amyloid β (Aβ) pathology, and cognitive function in male castrated App (App) mice. We found significantly reduced androgen receptor (AR/Ar) expression levels in the precunei of male patients with early AD pathology and isolated brain microglia of male App mice compared with their nonpathological controls. In castrated App mice, microglial Tnf and Il6 and astrocytic Socs3 were downregulated, indicating that androgens may promote inflammation in the brain. However, Aβ accumulation and cognitive function were unaffected. These results suggest that although systemic androgen deprivation modulates neuroinflammation, the changes are insufficient to alter the AD phenotype or pathology in male App mice.
© 2025. The Author(s).

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ABOUT THE EXPERTS

Kasumi Maekawa,Akira Sobue,Okiru Komine,Yuko Saito,Shigeo Murayama,Takaomi C Saido,Takashi Saito,Koji Yamanaka

Kasumi Maekawa

Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Aichi, 464-8601, Japan.

Department of Neuroscience and Pathobiology, Nagoya University Graduate School of Medicine, Aichi, 466-8550, Japan.

Akira Sobue

Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Aichi, 464-8601, Japan.

Department of Neuroscience and Pathobiology, Nagoya University Graduate School of Medicine, Aichi, 466-8550, Japan.

Medical Interactive Research and Academia Industry Collaboration Center, Research Institute of Environmental Medicine, Nagoya University, Aichi, 464-8601, Japan.

Okiru Komine

Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Aichi, 464-8601, Japan.

Department of Neuroscience and Pathobiology, Nagoya University Graduate School of Medicine, Aichi, 466-8550, Japan.

Yuko Saito

Department of Neuropathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, 173-0015, Japan.

Shigeo Murayama

Brain Bank for Aging Research, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, 173-0015, Japan.

Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development, Osaka University, Osaka, Japan.

Takaomi C Saido

Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, 351-0198, Japan.

Takashi Saito

Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Aichi, 464-8601, Japan.

Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Aichi, 467-8601, Japan.

Koji Yamanaka

Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Aichi, 464-8601, Japan. yamanaka.koji.p4@f.mail.nagoya-u.ac.jp.

Department of Neuroscience and Pathobiology, Nagoya University Graduate School of Medicine, Aichi, 466-8550, Japan. yamanaka.koji.p4@f.mail.nagoya-u.ac.jp.

Institute for Glyco-core Research (iGCORE), Nagoya University, Aichi, Japan. yamanaka.koji.p4@f.mail.nagoya-u.ac.jp.

Center for One Medicine Innovative Translational Research (COMIT), Nagoya University, Aichi, Japan. yamanaka.koji.p4@f.mail.nagoya-u.ac.jp.

Research Institute for Quantum and Chemical Innovation, Institutes of Innovation for Future Society, Nagoya University, Aichi, Japan. yamanaka.koji.p4@f.mail.nagoya-u.ac.jp.