title: Phosphorylated Smad 2/3 colocalizes with phospho-tau inclusions in Pick disease, progressive supranuclear palsy, and corticobasal degeneration but not with alpha-synuclein inclusions in multiple system atrophy or dementia with Lewy bodies.
abstract: Impaired transduction of transforming growth factor-beta signaling has recently been implicated in Alzheimer disease. Transforming growth factor-beta signals are transduced by Smads, which are phosphorylated and translocated to the nucleus, where they initiate gene transcription. In Alzheimer disease, neurofibrillary tangles sequester phosphorylated Smad 2/3 (pSmad2/3) and reduce its nuclear translocation. We have now investigated the relationship between pSmad2/3 and phospho-tau in 3 other tauopathies, Pick disease, progressive supranuclear palsy, and corticobasal degeneration, and in 2 alpha-synucleinopathies, dementia with Lewy bodies and multiple system atrophy. In Pick disease, progressive supranuclear palsy, and corticobasal degeneration, pSmad2/3 was demonstrated in neuronal and glial nuclei but also colocalized with cytoplasmic tau inclusions. No pSmad2/3 was detected in glial cytoplasmic inclusions in multiple system atrophy or in Lewy bodies in dementia with Lewy bodies. Our data indicate that phospho-tau but not alpha-synuclein cytoplasmic inclusions bind pSmad2/3. The preservation of neuronal nuclear pSmad2/3 in Pick disease, progressive supranuclear palsy, and corticobasal degeneration suggests that cytoplasmic sequestration of pSmad2/3 is likely to have less impact on transforming growth factor-beta signal transduction in these diseases than in Alzheimer disease.
authors.affiliation: Dementia Research Group, University of Bristol Institute of Clinical Neurosciences, Department of Clinical Science at North Bristol, Frenchay Hospital, Bristol, BS16 1LE, UK.
authors.forename: Katy A
authors.initials: KA
authors.lastname: Chalmers
authors.forename: Seth
authors.initials: S
authors.lastname: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism*; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology; D008297:Male; D019578:Multiple System Atrophy / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D020774:Pick Disease of the Brain / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D051785:Smad Proteins / Q000378:metabolism*; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D051844:alpha-Synuclein; D016875:tau Proteins