title: Cofilin rods and aggregates concur with tau pathology and the development of Alzheimer's disease.
abstract: BACKGROUND
  Imaging of human brain as well as cellular and animal models has highlighted a role for the actin cytoskeleton in the development of cell pathology in Alzheimer's disease (AD). Rods and aggregates of the actin-associated protein cofilin are abundant in grey matter of postmortem AD brain and rods are found inside neurites in animal and cell models of AD.
  
  
  OBJECTIVE
  We sought further understanding of the significance of cofilin rods/aggregates to the disease process: Do rods/aggregates correlate with AD progression and the development of hallmark neurofibrillary tangles and neuropil threads? Are cofilin rods/aggregates found in the same neurites as hyperphosphorylated tau?
  
  
  METHODS
  The specificity of rods/aggregates to AD compared with general aging and their spatial relationship to tau protein was examined in postmortem human hippocampus, inferior temporal cortex, and anterior cingulate cortex.
  
  
  RESULTS
  The presence of cofilin rods/aggregates correlated with the extent of tau pathology independent of patient age. Densities of rods/aggregates were fourfold greater in AD compared with aged-matched control brains and rods/aggregates were significantly larger in AD brain. We did not find evidence for our hypothesis that intracellular cofilin rods are localized to tau-positive neuropil threads. Instead, data suggest the involvement of microglia in the clearance of cofilin rods/aggregates and/or in their synthesis in and around amyloid plaques and surrounding neuropil.
  
  
  CONCLUSIONS
  Cofilin rods and aggregates signify events initiated early in the pathological cascade. Further definition of the mechanisms leading to their formation in the human brain will provide insights into the cellular causes of AD.
authors.affiliation: The Brain & Mind Research Institute, University of Sydney, Sydney, Australia Discipline of Anatomy and Histology, School of Medical Sciences, University of Sydney, Sydney, Australia.
authors.forename: Tasnim
authors.initials: T
authors.lastname: Rahman
authors.affiliation: The Brain & Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Davies
authors.affiliation: Centre for Psychiatry and Clinical Neuroscience, School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Rudi K
authors.initials: RK
authors.lastname: Tannenberg
authors.affiliation: The Brain & Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fok
authors.affiliation: Neuroscience Research Australia and the University of New South Wales, Sydney, NSW, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Shepherd
authors.affiliation: Centre for Psychiatry and Clinical Neuroscience, School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dodd
authors.affiliation: Discipline of Anatomy and Histology, School of Medical Sciences, University of Sydney, Sydney, Australia.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Cullen
authors.affiliation: The Brain & Mind Research Institute, University of Sydney, Sydney, Australia Discipline of Anatomy and Histology, School of Medical Sciences, University of Sydney, Sydney, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Goldsbury
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D008875:Middle Aged; D016875:tau Proteins / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C054369:MAPT protein, human; C046643:alpha-internexin; D016875:tau Proteins
keywords: Actin; amyloid plaque; cofilin protein; cytoskeleton; microglia; neurofibrillary tangles; neuropil threads; tau protein