title: Selective vulnerability in neurodegeneration: insights from clinical variants of Alzheimer's disease.
abstract: 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.
authors.affiliation: Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Nuffield Department of Clinical Neurosciences, Oxford University, Oxford, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Turner
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000473:pathology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D010641:Phenotype; D058225:Plaque, Amyloid / Q000473:pathology
keywords: ALZHEIMER'S DISEASE