Complex tauopathies vs. tangle predominant dementia : Response to the Letter from Professor Kurt Jellinger.

Institute of Neurology, Medical University Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria, .
Acta Neuropathologica (Impact Factor: 10.76). 09/2011; DOI: 10.1007/s00401-011-0870-7
Source: PubMed
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    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.
    Acta Neuropathologica 03/2011; 122(2):205-22. DOI:10.1007/s00401-011-0819-x · 10.76 Impact Factor
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    ABSTRACT: Limbic neurofibrillary tangle dementia (LNTD) is a subset of senile dementia characterized by numerous neurofibrillary tangles (NFT) in the hippocampal area, although there is an absence or scarcity of amyloid deposits (AM) throughout the brain. In the present study, we immunohistochemically investigated regional numbers and tau isoforms of NFT in the hippocampal area of nine LNTD patients with anti-three-repeat (3R) tau-specific and anti-four-repeat (4R) tau-specific antibodies, differentiating NFT into three developmental stages of pretangles (PT), NFT and ghost tangles (GT). Consequently, most PT were 4R tau-positive, most GT were 3R tau-positive, and NFT were 3R tau-, 4R tau- or double-positive, suggesting that composition of tau isoforms may shift from a 4R tau-predominant pattern to a 3R tau-predominant pattern during the development of NFT. In addition, a large number of NFT showing different developmental stages and different rates of 3R tau- and 4R tau-positive neurons according to the region were found in the hippocampal area, suggesting that regions undergoing earlier NFT formation may show higher ratio of 3R tau-positive neurons to 4R tau-positive neurons, and that NFT formation may begin in the entorhinal and transentorhinal cortices, subsequently progress to the subiculum and CA1, and further to the CA2, amygdala and CA3-4, although progression to the neocortex is limited. Furthermore, 4R tau-positive astrocytes and grains were found in several patients, suggesting that LNTD is a form of tauopathy.
    Neuroscience Letters 10/2006; 405(1-2):29-33. DOI:10.1016/j.neulet.2006.06.036 · 2.03 Impact Factor
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    ABSTRACT: Neurofibrillary tangle predominant dementia (NFTPD) is a subset of late onset dementia, clinically different from traditional "plaque and tangle" Alzheimer disease (AD): later onset, shorter duration, less severe cognitive impairment, and almost absence of ApoE epsilon4. Neuropathology reveals abundant allocortical neurofibrillary pathology with no or few isocortical tau lesions, absence of neuritic plaques, absence or scarcity of amyloid deposits, but neurofibrillary changes comprising both 3 and 4 repeat (3R and 4R) tau immunohistochemistry are not significantly different from those in classical AD. Comparing 51 autopsy cases of NFTPD with 244 classical AD subjects, the nosology of NFTPD and its differences from AD are discussed.
    Acta Neuropathologica 03/2007; 113(2):107-17. DOI:10.1007/s00401-006-0156-7 · 10.76 Impact Factor


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