Guest Editors
Dr. Brad T. Casali
Email: bcasali@neomed.edu
Affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, OH 44272, USA.
Research Interests: microglia, sex chromosomes, neuroinflammation, APOE, neurodegenerative diseases
Summary
Sex as a biological variable plays a crucial role in the onset, progression, and severity of many diseases, including neurodegenerative disorders. Alzheimer's disease (AD) exhibits a striking sex bias, with women disproportionately affected both in prevalence and clinical severity. Despite extensive research into AD pathology—encompassing neuronal loss, amyloid plaque deposition, tau pathology, and neuroinflammation—the molecular and cellular mechanisms underlying these sex differences remain poorly defined. This special issue seeks to illuminate the complex interplay between sex-specific factors and neurodegenerative processes, with an emphasis on molecular and cellular insights relevant to AD.
We welcome original research and comprehensive reviews that cover mechanistic, preclinical, and translational studies addressing:
1. Molecular and Cellular Mechanisms of Sex Differences in AD: Investigations into how sex chromosomes, epigenetic regulation, and hormonal influences affect neuronal resilience, amyloid and tau pathology, and synaptic function.
2. Microglial Biology and Neuroinflammation: Studies elucidating sex-specific roles of microglia and other myeloid cells in AD pathogenesis, including differential activation states, receptor signaling, and their impact on neurodegenerative progression.
3. APOE Isoforms and Sex-Dependent Risk Factors: Research exploring the molecular basis of increased AD susceptibility in women carrying the APOE4 allele, and how this influences lipid metabolism, immune responses, and amyloid clearance.
4. Metabolic and Gut-Brain Axis Contributions: Insights into sex differences in brain metabolism, cerebrovascular function, and microbiota-mediated modulation of tau pathology and neuroinflammation.
5. Therapeutic Targets and Personalized Medicine: Preclinical and translational studies assessing sex-specific efficacy of treatments targeting neuroinflammation, metabolic pathways, or genetic risk factors, toward tailored interventions.
By integrating findings across molecular, cellular, and systemic scales, this issue aims to deepen understanding of how sex influences AD pathophysiology and to accelerate the development of sex-informed therapeutic strategies.
Keywords
sex differences, Alzheimer's disease, microglia, APOE4, neuroinflammation, metabolism, gut-brain axis, neurodegeneration
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