Copathology in Progressive Supranuclear Palsy: Does It Matter?

Area of Science:

• Neuroscience
• Neuropathology
• Clinical Neurology

Background:

• The impact of co-occurring brain pathologies on the progression rate of progressive supranuclear palsy (PSP) is not well understood.
• Investigating these co-pathologies is crucial for understanding PSP's complex nature.

Purpose of the Study:

• To determine the frequency and severity of co-pathologies in PSP patients.
• To analyze how these co-pathologies influence the progression of PSP.

Main Methods:

• Clinic-pathological analysis of 101 PSP patients.
• Standardized criteria used to diagnose and stage co-pathologies (e.g., Alzheimer's disease, argyrophilic grains, Lewy-related pathology, TDP-43, FUS, CAA, SVD).
• Extracted demographic data and clinical milestones.

Main Results:

• Pure PSP pathology was rare (8%); most patients had co-pathologies.
• Alzheimer's disease pathology (84%) and argyrophilic grains (58%) were most frequent.
• Small vessel disease was common (65%); other co-pathologies were rare.
• Co-pathologies were generally mild, except for widespread argyrophilic grains.
• Co-pathologies did not significantly impact disease milestones or progression rate.

Conclusions:

• Concomitant pathologies in PSP are frequent but typically mild.
• Four repeat tau remains the key therapeutic target in PSP.
• Co-pathologies have minimal impact on PSP progression, guiding future therapy development.