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01-08-2011 | Original Paper

A peculiar constellation of tau pathology defines a subset of dementia in the elderly

Authors: Gabor G. Kovacs, Kinga Molnár, Lajos László, Thomas Ströbel, Gergö Botond, Selma Hönigschnabl, Angelika Reiner-Concin, Miklós Palkovits, Peter Fischer, Herbert Budka

Published in: Acta Neuropathologica | Issue 2/2011

Abstract

Sporadic tauopathies are characterized by differential cellular and topographical predominance of phospho-tau immunoreactivity and biochemical distinction of the tau protein. Established entities include progressive supranuclear palsy, corticobasal degeneration, Pick’s disease, and argyrophilic grain disease. During a community-based longitudinal study on aging, we detected tau pathologies not compatible with these categories. We immunostained for different phospho-tau epitopes, 4R and 3R tau isoforms, α-synuclein, amyloid-β, and phospho-TDP-43, analyzed the MAPT and ApoE genes, and performed western blotting for the tau protein. The mean age of patients (4 women, 3 men) was 83.8 years. Clinical presentations combined dementia with psychiatric symptoms and/or parkinsonism. In addition to neurofibrillary tangles and diffuse neuronal cytoplasmic tau immunoreactivity, the neuropathology was characterized by peculiar cytopathologies (diffuse granular immunopositivity of astrocytic processes and patchy accumulation of thin threads) in a distinctive distribution (frontal and temporal cortices, hippocampus, amygdala, basal ganglia, locus coeruleus, and substantia nigra). Argyrophilic grains were detected in four patients. Few to moderate densities of neuritic plaques but widespread phospho-TDP-43 pathology was observed in five patients. There was variability in the H1/H2 and ApoE alleles and biochemical features of tau protein. We propose these cases as complex tauopathy with a characteristic constellation: some features of primary tauopathies and Alzheimer’s disease mixed with additional cytopathologies including a distinctive astrogliopathy, in a characteristic distribution of lesions. These complex tauopathies in the elderly deserve specific diagnostic and eventually therapeutic considerations.

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Title: A peculiar constellation of tau pathology defines a subset of dementia in the elderly
Authors: Gabor G. Kovacs
Kinga Molnár
Lajos László
Thomas Ströbel
Gergö Botond
Selma Hönigschnabl
Angelika Reiner-Concin
Miklós Palkovits
Peter Fischer
Herbert Budka
Publication date: 01-08-2011
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 2/2011
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-011-0819-x

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A peculiar constellation of tau pathology defines a subset of dementia in the elderly

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