Internalization of tau antibody and pathological tau protein detected with a flow cytometry multiplexing approach
| Autor: | Suhail Rasool, Nina Helen Rosenqvist, Einar M. Sigurdsson, Dov B. Shamir, Jan Torleif Pedersen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Epidemiology media_common.quotation_subject Tau protein Blotting Western tau Proteins Antibodies Article Flow cytometry 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Developmental Neuroscience Western blot Alzheimer Disease Neuroblastoma mental disorders medicine Animals Humans Phosphorylation Internalization media_common Neurons biology medicine.diagnostic_test Chemistry Health Policy Brain Neurofibrillary Tangles Transfection medicine.disease Flow Cytometry Molecular biology Psychiatry and Mental health 030104 developmental biology biology.protein Neurology (clinical) Geriatrics and Gerontology Antibody 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer'sdementia : the journal of the Alzheimer's Association. 12(10) |
| ISSN: | 1552-5279 |
| Popis: | Introduction Tau immunotherapy has emerged as a promising approach to clear tau aggregates from the brain. Our previous findings suggest that tau antibodies may act outside and within neurons to promote such clearance. Methods We have developed an approach using flow cytometry, a human neuroblastoma cell model overexpressing tau with the P301L mutation, and paired helical filament (PHF)–enriched pathologic tau to effectively screen uptake and retention of tau antibodies in conjunction with PHF. Results The flow cytometry approach correlates well with Western blot analysis to detect internalized antibodies in naive and transfected SH-SY5Y cells (r 2 = 0.958, and r 2 = 0.968, P = .021 and P = .016, respectively). In transfected cells, more antibodies are taken up/retained as pathologic tau load increases, both under co-treated conditions and when the cells are pretreated with PHF before antibody administration (r 2 = 0.999 and r 2 = 0.999, P = .013 and P = .011, respectively). Discussion This approach allows rapid in vitro screening of antibody uptake and retention in conjunction with pathologic tau protein before more detailed studies in animals or other more complex model systems. |
| Databáze: | OpenAIRE |
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