Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Distinct TDP-43 aggregate features and toxicity stratify FTD patients
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    Laferriere F, Maniecja Z, Perez-Berlanga M, Hruska-Plochan M, Larissa G, Hock E-M, Wagner U, Afroz T, Boersema PJ, Barmettler G, Foti S, Asi Y, Isaacs A, Al-Amoudi A, Lewis A, Henning S, Ravits J, De Giorgi F, Ichas F, Erwan B, Paola P, Lashley TC, Polymenidou M
  • Publisher:
    Nature Publishing Group
  • Publication date:
  • Journal:
    Nature Neuroscience
  • Print ISSN:
Accumulation of abnormally phosphorylated TDP-43 (pTDP-43) is the main pathology in affected neurons of patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Morphological diversity and neuroanatomical distribution of pTDP-43 accumulations allowed classification of FTD cases into at least four different subtypes, which correlate with clinical presentations and genetic causes. To understand the molecular basis of this heterogeneity, we developed SarkoSpin, a new method for extremely pure biochemical isolation of pathological TDP-43. Combining SarkoSpin with mass spectrometry, we revealed proteins beyond TDP-43, which become abnormally insoluble in a disease subtype-specific manner. We show that pTDP-43 extracted from disease brain forms large and stable assemblies of distinct densities and morphologies that correlate with disease subtypes. Importantly, biochemically extracted pTDP-43 assemblies displayed differential neurotoxicity and seeding that correlated with disease duration of FTLD patients. Our data indicate that disease heterogeneity may originate from alternate pathological TDP-43 conformations, eminiscent of prion strains.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Neurodegenerative Diseases
Neurodegenerative Diseases
Neurodegenerative Diseases
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by