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

Similarities between frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa (TDP-43) (FTLD-TDP) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) raise questions about whether they represent distinct entities or a single disease spectrum. The literature mostly examined series with disproportionate numbers of LATE-NC over FTLD-TDP.

Leveraging a clinicopathological collection of FTLD-TDP (N = 148) from the University of California, San Francisco, we compared demographic, clinical, genetic, and neuropathological features of FTLD-TDP, particularly FTLD-TDP type A (N = 39), and LATE-NC (N = 42).

FTLD-TDP type A cases were younger at onset and death, had shorter disease duration, and frequent genetic causes (GRN, C9ORF72) compared to LATE-NC, which were mostly sporadic and older. Blinded evaluation of middle frontal gyrus (MFG) TDP-43 immunostaining alone proved insufficient to reliably differentiate FTLD-TDP type A from LATE-NC stage 3. However, factoring in all neuropathologic features, FTLD type A and LATE-NC could be differentiated with >95% confidence.

These overall findings support distinct diagnostic entities for FTLD-TDP and LATE-NC.