LATE-NC staging in routine neuropathologic diagnosis: an update

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• Geriatric Medicine

Background:

• The 2019 consensus report established a classification for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC).
• Existing LATE-NC criteria are useful but require updates to address diagnostic challenges and unusual presentations.
• Dementia research and autopsy practice necessitate refined diagnostic standards for TDP-43 proteinopathies.

Purpose of the Study:

• To update neuropathologic criteria for diagnosing and staging LATE-NC based on published data.
• To provide guidance on integrating genetic information and comorbid pathologies (e.g., ADNC, Lewy body disease) into LATE-NC diagnosis.
• To clarify differentiation of LATE-NC from other TDP-43 pathologies (FTLD, ALS) and address atypical cases.

Main Methods:

• Review and synthesis of published literature on LATE-NC and related TDP-43 proteinopathies.
• Analysis of diagnostic criteria and staging schemes for LATE-NC.
• Integration of findings on genetic factors and comorbid neuropathologies.

Main Results:

• Updated neuropathologic criteria for LATE-NC diagnosis and staging are proposed.
• Practical recommendations are provided for incorporating genetic data and comorbid conditions like ADNC.
• Guidance is offered for differentiating LATE-NC from FTLD and ALS, and for diagnosing unusual TDP-43 pathology presentations.

Conclusions:

• The updated criteria aim to improve the precision of LATE-NC staging and diagnosis.
• Recommendations address the integration of comorbid pathologies and genetic information for comprehensive assessment.
• Further research is needed to resolve remaining questions and refine understanding of LATE-NC and TDP-43 pathology.