Quantifying regional α -synuclein, amyloid β, and tau accumulation in lewy body dementia.

Autor: Miller RL; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO., Dhavale DD; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO., O'Shea JY; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO., Andruska KM; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO., Liu J; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO., Franklin EE; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Buddhala C; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO., Loftin SK; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Department of Radiology, Washington University School of Medicine, St. Louis, MO., Cirrito JR; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO., Perrin RJ; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Cairns NJ; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.; College of Medicine and Health, University of Exeter, Exeter, United Kingdom., Campbell MC; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO.; Department of Radiology, Washington University School of Medicine, St. Louis, MO., Perlmutter JS; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Department of Radiology, Washington University School of Medicine, St. Louis, MO.; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO.; Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO.; Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO., Kotzbauer PT; Department of Neurology, Washington University School of Medicine, St. Louis, MO.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO.; Developmental Biology, Washington University School of Medicine, St. Louis, MO.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2022 Feb; Vol. 9 (2), pp. 106-121. Date of Electronic Publication: 2022 Jan 21.
DOI: 10.1002/acn3.51482
Abstrakt: Objective: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid β (Aβ) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aβ, and tau accumulation in neocortical, limbic, and basal ganglia regions.
Methods: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble α-syn, Aβ, and tau with recently developed sandwich ELISAs.
Results: We detected a wide range of insoluble α-syn accumulation in LBD cases. The majority had substantial α-syn accumulation in most regions, and dementia severity correlated with neocortical α-syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial Aβ accumulation, although the mean Aβ level in LBD was lower than in AD. The presence of Aβ was associated with greater α-syn accumulation. Tau accumulation accompanied Aβ in only one LBD case.
Interpretation: LBD is associated with insoluble α-syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between Aβ and α-syn accumulation suggests a pathophysiologic relationship between these two processes.
(© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje