title: Distinctive pathological mechanisms involved in primary progressive aphasias.
abstract: Primary progressive aphasia (PPA) comprises a heterogeneous group of neurodegenerative conditions that can be classified in three cliniconeuroanatomic syndromes. Limited information exists, however, about patterns of neuropathologic spreading and microscopic changes underpinning each syndrome. We performed an analysis of a longitudinal in vivo cohort and a postmortem PPA cohort to investigate neurodegeneration over time and to quantify microscopic changes in key language brain areas. The longitudinal analyses demonstrated distinctive patterns of topological extension of brain atrophy. Although semantic variant (sv-PPA) showed an eccentric pattern, nonfluent and/or agrammatic (nfv-PPA) and logopenic (lv-PPA) variants showed additional multifocal extension. The quantitative pathology showed that sv-PPA had neuronal loss and thinning in BA 38, whereas nfv-PPA showed thinning in BA 44/45 and evidence of microscopic involvement in BA 40/22. Although lv-PPA showed neuronal loss focused on BA 40/22, imaging results demonstrated widespread left-sided brain atrophy. These analyses provide an account of the pathologic process whereby each variant has stereotypical patterns of brain atrophy extension, which is largely determined by the specific pathologic type.
authors.affiliation: Faculty of Health Sciences, The University of Sydney, Lidcombe, New South Wales, Australia; Neuroscience Research Australia, Randwick, New South Wales, Australia; ARC Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia. Electronic address: cristian.leyton@sydney.edu.au.
authors.forename: Cristian E
authors.initials: CE
authors.lastname: Leyton
authors.affiliation: Department of Pathology, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Britton
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; ARC Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia; School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia; School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: Department of Pathology, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jillian J
authors.initials: JJ
authors.lastname: Kril
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D018888:Aphasia, Primary Progressive / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged
keywords: Alzheimer's disease; Frontotemporal dementia; Logopenic variant; Nonfluent/agrammatic variant; Primary progressive aphasia; Quantitative pathology; Semantic variant