Primary Progressive Aphasia-Defining Genetic and Pathological Subtypes

J.      D. Rohrer; J.      M. Schott

Abstract

The primary progressive aphasias (PPA) are a group of clinically, genetically and pathologically heterogeneous neurodegenerative disorders caused by FTLD-tau, FTLD-TDP or Alzheimers disease pathology. Clinically, three subtypes are recognized, the semantic, logopenic and nonfluent variants but there remains ongoing discussions over how the clinical subtypes should be dissected. This review looks at the genetic and pathological basis of PPA and argues that with the advent of clinical trials in PPA, establishing the underlying pathology accurately during life will become increasingly important. Current and future biomarkers that may help make a pathological diagnosis in life, i.e. PPA-tau, PPA-TDP and PPA-AD, are reviewed including clinical and neuropsychological data, neuroimaging, blood and CSF markers.

Keywords: Primary progressive aphasia, progressive nonfluent aphasia, ntic dementia, logopenic aphasia, frontotemporal dementia, frontotemporal lobar degeneration, tau, TDP-43, progranulin, Mesulam, corticobasal syndrome, progressive supranuclear palsy, semantic variant, logopenic variant, nonfluent variant