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P4–123: PrP Sc Aggregates in the ocular lens of symptomatic and pre–symptomatic prion infected mice
Author(s) -
Prelli Frances,
Pankiewicz Joanna,
Moncaster Juliet,
Klunk William,
Carp Richard,
Meeker Harry,
Sadowski Martin,
Goldstein Lee E.,
Wisniewski Thomas
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1862
Subject(s) - western blot , ex vivo , cataracts , in vivo , genetically modified mouse , pathology , amyloid (mycology) , biology , lens (geology) , immunohistochemistry , neurodegeneration , chemistry , fatal familial insomnia , microbiology and biotechnology , prion protein , virology , transgene , medicine , biochemistry , disease , paleontology , genetics , gene
aphasias. Unfortunately, current clinical classifications of degenerative aphasias correlate poorly with underlying pathological and biochemical features of disease. Objective(s): To determine whether modification of current clinical classifications of degenerative aphasias, including the explicit identification of AOS as a seperate entity, would improve correlation with underlying pathology, and to identify imaging characteristics of AOS. Methods: Sixteen cases with an initial clinical diagnosis of degenerative aphasia or AOS that came to postmortem examination were retrospectively reclassified independently by two speech-language pathologists blinded to pathologic and biochemical findings into one of five operationally defined categories of aphasia and AOS. All cases were also independently classified as either “tauopathy” or “non-tauopathy.” Voxel-based morphometry was applied to assess patterns of atrophy in AOS on MRI, and clinico-imaging and clinico-pathological associations were sought. Results: Biochemical classification was 11 tauopathy and 5 non-tauopathy. Tauopathies included progressive supranuclear palsy (n 5), corticobasal degeneration (n 5), and Pick’s disease (n 1). All non-tauopathies were characterized by the presence of tau and alpha-synuclein negative, but ubiquitin-positive inclusions (FTLD-U). Interjudge speech-language clinical classification reliability was 86% for all evaluations ( 0.8). Ten cases had evidence of AOS, of which all were classified as tauopathy. Five of the six cases without AOS were classified as non-tauopathy (p 0.001). A majority of the cases had more than one yearly evaluation, demonstrating evolution of the speech and language syndromes, as well as motor signs. In many cases, parkinsonism and limb apraxia developed later in the disease course. The premotor and supplemental motor cortices were the main cortical regions associated with AOS (Figure). Conclusions: Our refinement of the classification of degenerative aphasias and AOS significantly improved clinico-pathological correlation and may help to better our understanding of the relationships among behavioral, pathological, and imaging characteristics. The presence of AOS suggests underlying tau pathology.