Evaluating the updated LATE-NC staging criteria using data from NACC.

Area of Science:

• Neuropathology
• Neuroscience
• Gerontology

Background:

• Updated staging criteria for limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) were released in 2023.
• This study evaluates the 2023 LATE-NC staging criteria using data from the National Alzheimer's Coordinating Center.

Purpose of the Study:

• To assess the validity and clinical relevance of the updated LATE-NC staging criteria.
• To examine the associations between LATE-NC stages, cognitive function, and other neuropathologic changes.

Main Methods:

• Utilized multilevel regression models to analyze associations between LATE-NC stages and cognitive outcomes.
• Examined relationships between LATE-NC stages and other neuropathologic changes, including hippocampal sclerosis of aging (HS-A), Alzheimer's disease NC (ADNC), and Lewy bodies (LBs).

Main Results:

• Of 1352 participants, 37% exhibited LATE-NC, with stage 2 being the most prevalent (58%).
• All LATE-NC stages were significantly associated with cognitive impairment, even after accounting for other neuropathologic changes.
• LATE-NC stage 1b, present in 22% of stage 1 cases, showed distinct associations, being linked to cognition and HS-A but not ADNC or LBs.

Conclusions:

• The updated LATE-NC staging criteria effectively differentiate patterns of TDP-43 proteinopathy spread and their cognitive consequences.
• LATE-NC stage 1b represents an early stage of TDP-43 pathology with specific associations, highlighting the nuances captured by the updated criteria.