Cofilin rods and aggregates concur with tau pathology and the development of alzheimer's disease

Rahman, Tasnim, Davies, Danielle S., Tannenberg, Rudi K., Fok, Sandra, Shepherd, Claire, Dodd, Peter R., Cullen, Karen M. and Goldsbury, Claire (2014) Cofilin rods and aggregates concur with tau pathology and the development of alzheimer's disease. Journal of Alzheimer's Disease, 42 4: 1443-1460. doi:10.3233/JAD-140393


Author Rahman, Tasnim
Davies, Danielle S.
Tannenberg, Rudi K.
Fok, Sandra
Shepherd, Claire
Dodd, Peter R.
Cullen, Karen M.
Goldsbury, Claire
Title Cofilin rods and aggregates concur with tau pathology and the development of alzheimer's disease
Journal name Journal of Alzheimer's Disease   Check publisher's open access policy
ISSN 1875-8908
1387-2877
Publication date 2014-10-13
Year available 2014
Sub-type Article (original research)
DOI 10.3233/JAD-140393
Open Access Status
Volume 42
Issue 4
Start page 1443
End page 1460
Total pages 18
Place of publication Amsterdam, Netherlands
Publisher I O S Press
Collection year 2015
Language eng
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. Conclusion: 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.
Keyword Actin
Amyloid plaque
Cofilin protein
Cytoskeleton
Microglia
Neurofibrillary tangles
Neuropil threads
Tau protein
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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