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Selective vulnerability in neurodegeneration: insights from clinical variants of Alzheimer's disease
  1. Niklas Mattsson1,
  2. Jonathan M Schott2,
  3. John Hardy3,
  4. Martin R Turner4,
  5. Henrik Zetterberg3,5
  1. 1Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden
  2. 2Dementia Research Centre, UCL Institute of Neurology, London, UK
  3. 3Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
  4. 4Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK
  5. 5Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden
  1. Correspondence to Dr Henrik Zetterberg, Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, Mölndal S-431 80, Sweden; henrik.zetterberg{at}


Selective vulnerability in the nervous system refers to the fact that subpopulations of neurons in different brain systems may be more or less prone to abnormal function or death in response to specific types of pathological states or injury. The concept has been used extensively as a potential way of explaining differences in degeneration patterns and the clinical presentation of different neurodegenerative diseases. Yet the increasing complexity of molecular histopathology at the cellular level in neurodegenerative disorders frequently appears at odds with phenotyping based on clinically-directed, macroscopic regional brain involvement. While cross-disease comparisons can provide insights into the differential vulnerability of networks and neuronal populations, we focus here on what is known about selective vulnerability-related factors that might explain the differential phenotypic expressions of the same disease—in this case, typical and atypical forms of Alzheimer's disease. Whereas considerable progress has been made in this area, much is yet to be elucidated; further studies comparing different phenotypic variants aimed at identifying both vulnerability and resilience factors may provide valuable insights into disease pathogenesis, and suggest novel targets for therapy.


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