Sex differences in alpha-synucleinopathies: a systematic review

Area of Science:

• Neuroscience
• Genetics
• Endocrinology

Background:

• Alpha-synucleinopathies manifest more severely in men, hinting at potential neuroprotection by female hormones like estrogen.
• The precise mechanisms behind these sex-based differences in alpha-synucleinopathies remain largely unknown.
• This systematic review critically assesses current evidence on sex and gender disparities in alpha-synucleinopathies.

Approach:

• A systematic review of studies published between 2012 and 2022 was conducted.
• Searches were performed across PubMed, Embase, and Ovid databases.
• Included studies focused on sex and gender differences in Rapid Eye Movement (REM) Behavior Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA).

Key Points:

• 162 studies were analyzed, covering RBD, MSA, DLB, and PD.
• Conclusive evidence supports sex- and gender-specific differences in demographics, biomarkers, genetics, clinical features, interventions, and quality of life.
• Research on sex hormone effects is limited, with a focus on estrogen's potential neuroprotective role.

Conclusions:

• Significant sex and gender differences exist across various alpha-synucleinopathies.
• Further research is crucial to elucidate sex-specific mechanisms.
• Understanding these mechanisms is vital for developing targeted, sex-specific therapies.