Abstract Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome that involves relentless development of aphasia with relative sparing of other cognitive functions, at least early in its course. There are multiple subtypes as well as multiple underlying pathologies. PPA and its subtypes can be difficult to differentiate from other neurodegenerative disorders and from each other, particularly early in their course. There are currently few clinical tools to assist in the early specific diagnosis of PPA and its subtypes. We have recently made substantial preliminary progress toward the development of novel imaging techniques that could be extremely valuable in early specific diagnosis of the molecular basis of specific pathologies underlying PPA. We propose to use tau and amyloid imaging tracers to attempt to discriminate these underlying molecular pathologies, and FDG-PET, functional connectivity MRI, and morphometric structural MRI to measure and longitudinally monitor markers of neurodegeneration in the language network(s) and other brain regions. In addition to more accurate diagnosis, these measures will likely be important for prognostication and monitoring of decline and the effects of putative therapies. The overall goal of this proposal is to translate these methods from new scientific technologies into clinically useful tools that can be used by clinicians around the country and internationally to improve the diagnostic specificity and assessment capabilities for PPA and its subtypes.