Transcriptomic analysis reveals suppression of steroidogenic acute regulatory protein in gender-specific differences in Alzheimer's disease

Pulak R Manna; Shengping Yang; P Hemachandra Reddy

doi:10.1016/j.bbadis.2025.167667

Transcriptomic analysis reveals suppression of steroidogenic acute regulatory protein in gender-specific differences in Alzheimer's disease

Biochim Biophys Acta Mol Basis Dis. 2025 Jan 12:167667. doi: 10.1016/j.bbadis.2025.167667. Online ahead of print.

Authors

Pulak R Manna¹, Shengping Yang², P Hemachandra Reddy³

Affiliations

¹ Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address: [email protected].
² Department of Biostatistics, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
³ Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

PMID: 39809368
DOI: 10.1016/j.bbadis.2025.167667

Abstract

Alzheimer's disease (AD)-related dementia preferentially impacts two-thirds of women and one-third of men. The steroidogenic acute regulatory (StAR) protein mediates the biosynthesis of neurosteroids that sustain diverse neuronal activities. Aging, involving neurosteroidal imbalance, is the predominant risk factor for AD causing dementia. Transcriptomic analysis, including clinical cognitive diagnosis (cogdx) stages, displays marked attenuation of StAR in brains of AD women than those of AD men, compared with cognitively normal (Non-AD) subjects. The present data provide the first evidence and new insights into the underly mechanisms exemplifying the suppression of StAR in gender-specific differences in AD.

Keywords: Alzheimer's disease; Gender-specificity; Neurosteroids; StAR; Transcriptome analysis.