TDP-43 pathology in primary lateral sclerosis.

Area of Science:

• Neuropathology
• Neurodegenerative Diseases

Background:

• Primary lateral sclerosis (PLS) is a debated motor neuron disease (MND) subtype.
• Its distinction from amyotrophic lateral sclerosis (ALS) remains unclear.
• Few neuropathological studies of PLS exist, especially using modern techniques.

Purpose of the Study:

• To investigate the neuropathological features of clinically defined PLS.
• To compare PLS pathology with amyotrophic lateral sclerosis (ALS).
• To determine if PLS is a distinct clinico-pathological entity.

Main Methods:

• Examined postmortem brain and spinal cord tissue from seven PLS cases.
• Utilized neuropathological techniques, including TDP-43 immunohistochemistry.
• Assessed degeneration in motor cortex, corticospinal tracts, and lower motor neurons (LMN).

Main Results:

• All cases showed chronic degeneration of the primary motor cortex and/or corticospinal tracts.
• TDP-43 immunoreactive (TDP-ir) pathology was found in the motor cortex (5/5 cases) and LMN (7/7 cases).
• LMN involvement was minimal, with rare TDP-ir inclusions, even in long-duration cases.

Conclusions:

• PLS and ALS share TDP-43 pathology, indicating a close relationship.
• Minimal LMN involvement suggests PLS is a distinct MND form with protected LMN.
• PLS represents a unique neurodegenerative profile within the MND spectrum.