Asymmetry and heterogeneity of Alzheimer’s and frontotemporal pathology in primary progressive aphasia

• DOI: 10.1093/brain/awu024
• Publication Date: 2014-02-27T01:25:23Z
• Authors: M.-Marsel Mesulam; Sandra Weintraub; Emily J. Rogalski; Christina Wieneke; Changiz Geula; Eileen H. Bigio
• Keywords: Primary progressive aphasia; Frontotemporal lobar degeneration; Neuropathology

Fifty-eight autopsies of patients with primary progressive aphasia are reported.Twenty-three these were previously described (Mesulam et al., 2008) but had their neuropathological diagnoses updated to fit current criteria.Thirty-five the cases new.Their clinical classification was guided as closely possible by 2011 consensus guidelines (Gorno-Tempini 2011).Tissue included Alzheimer's disease in 45% and frontotemporal lobar degeneration (FTLD) others, an approximately equal split between TAR DNA binding protein 43 proteinopathies tauopathies.The most common distinctive feature for all pathologies associated asymmetric prominence atrophy, neuronal loss, disease-specific proteinopathy language-dominant (mostly left) hemisphere.The pathology displayed multiple atypical features.Males tended predominate, neurofibrillary more intense hemisphere, Braak pattern hippocampo-entorhinal tilted favour neocortex, APOE e4 allele not a risk factor.Mean onset age under 65 FTLD well groups.The FTLD-TAR group youngest fastest progression whereas FTLD-tau groups did differ from each other either or rate.Each cellular type preferred invariant presentation.The aphasic manifestation logopenic Alzheimer agrammatic FTLD-tau.The supranuclear palsy subtype consistently caused prominent speech abnormality together agrammatism C led semantic aphasia.The presence made very unlikely word comprehension impairment unlikely.The association much modest than has been implied results vivo amyloid imaging studies.Individual features aphasia, such impairment, informative underlying laborious diagnoses.At single patient level, no pathognomonic specific neuropathology type, highlighting critical role biomarkers diagnosing disease.During subtyping, some unclassifiable others simultaneously two subtypes.Revisions criteria proposed address challenges.