Neurodegeneration: 2023 update.

Area of Science:

• Neuroscience
• Neuropathology
• Genomics

Background:

• The field of neuropathology continually advances through human tissue-based research.
• Understanding neurodegenerative diseases requires diverse methodologies and disease category coverage.

Purpose of the Study:

• To review ten high-impact neuropathology studies from the past year.
• To emphasize human tissue-based research relevant to neuropathologists.
• To cover a broad spectrum of neurodegenerative disease research.

Main Methods:

• Integrated proteomic and transcriptomic analysis.
• Cryogenic electron microscopy (cryo-EM) for structural determination.
• Functional genomics and pathoanatomical studies.
• Application of deep learning in neuropathology.

Main Results:

• New diagnostic criteria for progressive supranuclear palsy.
• Insights into TAR DNA-binding protein 43 (TDP-43) roles in Alzheimer disease (AD) and limbic age-related TDP-43 encephalopathy (LATE).
• Cryo-EM revealed TMEM106B filaments in TDP-43 inclusions and prion protein amyloid structures.
• Microglial gene expression cataloged, APOE influence on chronic traumatic encephalopathy elucidated, and Lewy body progression pathways examined.
• Deep learning models applied to aging post-mortem brains.

Conclusions:

• Recent neuropathology research offers significant insights into neurodegenerative disease mechanisms.
• Advanced imaging and multi-omics approaches are revolutionizing structural and functional understanding.
• TDP-43 and TMEM106B are critical players in specific neurodegenerative pathways.
• Future research directions include integrating multi-omics data and deep learning for enhanced diagnostics.