FTLD-TDP versus LATE-NC: Experience of a Brain Bank specializing in FTLD-TDP

Area of Science:

• Neuropathology
• Neurodegenerative Diseases
• TDP-43 Proteinopathies

Background:

• Similarities between FTLD-TDP and LATE-NC create diagnostic ambiguity.
• Existing literature often overrepresents LATE-NC cases compared to FTLD-TDP.

Purpose of the Study:

• To compare FTLD-TDP (specifically type A) and LATE-NC using clinicopathological data.
• To determine if these conditions represent distinct entities or a disease spectrum.

Main Methods:

• Analysis of a clinicopathological cohort (N=148) from UCSF.
• Comparison of demographic, clinical, genetic, and neuropathological features of FTLD-TDP type A (N=39) and LATE-NC (N=42).

Main Results:

• FTLD-TDP type A cases were younger, had shorter disease duration, and more genetic causes (GRN, C9ORF72) than sporadic, older LATE-NC cases.
• TDP-43 immunostaining in the middle frontal gyrus alone was insufficient for differentiation.
• Combined neuropathological features allowed differentiation with >95% confidence.

Conclusions:

• FTLD-TDP and LATE-NC are distinct neuropathological entities.
• Comprehensive neuropathological assessment is crucial for accurate diagnosis.