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

Abstract INTRODUCTION 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. METHODS 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). RESULTS 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. DISCUSSION These overall findings support distinct diagnostic entities for FTLD‐TDP and LATE‐NC.