Figure 4. Clinicopathological and Genetic Associations in FTLD/ALS.

The schematic portrays relative frequencies of neuropathological subtypes of FTLD and pathogenic mutations associated with FTD clinical phenotypes arranged with predominant cognitive syndromes above and predominant motor disorders below (CBS is intermediate with largely mixed cognitive/motor features). Common associations between syndromes (i.e. ALS-bvFTD, PSP-naPPA) are identified with solid lines and dashed line represent less common co-morbid syndromes (i.e. ALS-naPPA, PSP-bvFTD, CBS-bvFTD). FTLD-Tau pathology (red) is found in virtually all PSP cases and the majority of naPPA. FTLD-Tau is also found in a significant proportion of CBS and bvFTD and rare in svPPA. TDP-43 pathology (blue) is found in almost all ALS and the majority of svPPA, while roughly half of bvFTD cased harbor FTLD-TDP at autopsy while FTLD-TDP pathology is less commonly found in naPPA and CBS. Atypical presentations of AD are seen in a significant proportion of CBS and less commonly in svPPA and naPPA, but very rarely in bvFTD. Finally, a small percentage of ALS has FUS or SOD-1 (green) pathology at autopsy and FUS is a rare substrate for bvFTD. Genetic etiologies linked to clinical phenotypes are written below in order of frequency; svPPA is largely a sporadic condition.