Figure 2. Clinicopathological correlations in tauopathies.

The scheme portrays (top) the relative frequencies of neuropathological subtypes of FTLD-Tau (i.e. primary tauopathies-red) and AD (i.e. secondary tauopathy-yellow) seen at autopsy in clinical phenotypes in FTD-spectrum disorders and aging by the color-coding of each box. Unremarkable neuropathological findings are shaded in green and TDP-43 protienopathies in blue (this schematic does not account for cerebrovascular changes, co-morbid pathology or less common neurodegenerative diseases). FTD clinical phenotypes are divided by cognitive and motor syndromes; the dashed line represents the clinical overlap between FTD cognitive and motor syndromes and CBS is placed intermediate to these categories as this clinical syndrome has aspects of both cognitive and motor dysfunction. AD neuropathology (yellow) is found in approximately a third of older patients who are cognitively normal (CN) and is seen in the majority amnestic AD clinical phenotype. FTLD-Tau (red) is found in virtually all PSPS cases and the majority of naPPA. FTLD-Tau is also found in a significant proportion of CBS and relatively rare in svPPA. Roughly half of bvFTD cases harbor FTLD-Tau while a small percentage can have AD neuropathology (yellow). Solid lines represent the predominant clinicopathological association for each specific tauopathy (bottom) while dashed lines represent less common clinical manifestations of each tauopathy. AD neuropathology is most commonly associated with the amnestic AD clinical phenotype but may also present as bvFTD, PPA variants and CBS. PART and AGD are largely associated with late onset (>80 years) amnestic syndrome similar to clinical AD and less commonly in CN individuals. PiD is most commonly found in association with bvFTD but can present with PPA variants or CBS. CBD tauopathy is primarily associated with CBS but also can manifest as bvFTD, naPPA or PSPS, while PSP is predominantly associated with PSPS and less commonly associated with naPPA or CBS.