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Neuronal network disintegration: common pathways linking neurodegenerative diseases
  1. Rebekah M Ahmed1,2,
  2. Emma M Devenney1,2,
  3. Muireann Irish2,3,
  4. Arne Ittner4,
  5. Sharon Naismith5,
  6. Lars M Ittner4,
  7. Jonathan D Rohrer6,
  8. Glenda M Halliday2,
  9. Andrew Eisen7,
  10. John R Hodges2,
  11. Matthew C Kiernan1
  1. 1Sydney Medical School Brain & Mind Centre, University of Sydney, Sydney, New South Wales, Australia
  2. 2Neuroscience Research Australia, University of NSW, Sydney, New South Wales, Australia
  3. 3School of Psychology, the University of New South Wales, Sydney, Australia
  4. 4Faculty of Medicine, Dementia Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia
  5. 5School of Psychology, Brain & Mind Centre, University of Sydney, Sydney, New South Wales, Australia
  6. 6Dementia Research Centre, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK
  7. 7University of British Columbia, Vancouver, British Columbia, Canada
  1. Correspondence to Dr Rebekah Ahmed, ForeFront, Brain and Mind Centre, University of Sydney, 94 Mallett St Camperdown, Sydney 2006, NSW, Australia; rebekah.ahmed{at}


Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration.


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  • Contributors RMA and MCK manuscript concept. All authors were involved in the drafting and editing of the manuscript.

  • Funding This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neurone disease, from the National Health and Medical Research Council of Australia (NHMRC) programme grant (#1037746 to GH, MK and JH) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Node (#CE110001021 JH) and other grants/sources (NHMRC project grant #1003139). RA is Royal Australasian College of Physicians PHD scholar and MND Research Australia PhD Scholar. MI is an ARC Discovery Early Career Researcher Award Fellow (#DE130100463). GH is a NHMRC Senior Principal Research Fellow (#1079679). LMI is a NHMRC Senior Research Fellow (#1003083). No funding source had a role in the writing of the manuscript.

  • Competing interests None declared.

  • Patient consent No.

  • Provenance and peer review Commissioned; externally peer reviewed.