Brainstem: neglected locus in neurodegenerative diseases

Area of Science:

• Neuroscience
• Neuropathology
• Gerontology

Background:

• Neurodegenerative diseases (NDs) like Alzheimer's (AD), Parkinson's (PD), and FTLD-TDP are characterized by protein deposits and neuronal death.
• Research has historically focused on supratentorial brain regions, linking deficits to telencephalic pathology.
• The brainstem's role in these diseases has been underestimated, particularly in FTLD-TDP.

Purpose of the Study:

• To review the impact of brainstem changes in common neurodegenerative diseases (PD, AD, FTLD-TDP).
• To highlight the under-researched involvement of the brainstem in FTLD-TDP.
• To emphasize the need for comprehensive studies on FTLD-TDP and brainstem pathology.

Main Methods:

• Literature review focusing on neuropathological studies of AD, PD, and FTLD-TDP.
• Analysis of recent findings on early-stage AD and PD, including brainstem nuclei involvement.
• Synthesis of existing research on brainstem pathology in FTLD-TDP.

Main Results:

• Early-stage AD and PD show significant, unexpected brainstem involvement.
• PD pathology involves degeneration of substantia nigra neurons, impacting dopamine pathways.
• FTLD-TDP exhibits more widespread brainstem pathology than previously recognized.

Conclusions:

• Brainstem involvement in AD and PD may necessitate revised concepts of disease origin, spread, and diagnosis.
• The extent of brainstem pathology in FTLD-TDP requires further investigation.
• Comprehensive research on FTLD-TDP, particularly brainstem changes, is urgently needed.