Cutaneous Phosphorylated Alpha-Synuclein in Lewy Body Dementia.

Area of Science:

• Neurology
• Biomarker Discovery
• Neurodegenerative Diseases

Background:

• Dementia with Lewy bodies (DLB) is a common neurodegenerative disorder.
• Accurate and early diagnosis of DLB remains a clinical challenge.
• Phosphorylated alpha-synuclein (P-SYN) is a key pathological hallmark of synucleinopathies.

Purpose of the Study:

• To evaluate the diagnostic performance of cutaneous P-SYN detection via skin biopsy.
• To assess P-SYN levels in patients with DLB, individuals with cognitive impairment (reduced MoCA), and healthy controls.

Main Methods:

• Subgroup analysis of the prospective, blinded Synuclein-One study (N=218).
• Skin biopsies were collected for P-SYN detection.
• Subjects included DLB patients meeting consensus criteria and control groups with normal or reduced Montreal Cognitive Assessment (MoCA) scores.

Main Results:

• Cutaneous P-SYN was detected in 96.0% of DLB patients (48/50).
• P-SYN was detected in 31% of controls with reduced MoCA (8/26).
• Only 3.3% of controls with normal MoCA showed P-SYN detection (4/120).

Conclusions:

• Skin biopsy detection of P-SYN demonstrates high sensitivity in clinically diagnosed DLB.
• P-SYN detection in skin may aid in diagnosing DLB, even in individuals with cognitive decline.
• This study supports the utility of P-SYN skin biopsies as a diagnostic tool for DLB.