Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements.

Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. Research Abstract Details 

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Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. Abstract Text:

Ayodeji A Asuni,Allal Boutajangout,David Quartermain,Einar M Sigurdsson,

Immunotherapies for various neurodegenerative diseases have recently emerged as a promising approach for clearing pathological protein conformers in these disorders. This type of treatment has not been assessed in models that develop neuronal tau aggregates as observed in frontotemporal dementia and Alzheimer's disease. Here, we present that active immunization with a phosphorylated tau epitope, in P301L tangle model mice, reduces aggregated tau in the brain and slows progression of the tangle-related behavioral phenotype. Females had more tau pathology than males but were also more receptive to the immunotherapy. The tau antibodies generated in these animals recognized pathological tau on brain sections. Performance on behavioral assays that require extensive motor coordination correlated with tau pathology in corresponding brain areas, and antibody levels against the immunogen correlated inversely with tau pathology. Interestingly, age-dependent autoantibodies that recognized recombinant tau protein but not the immunogen were detected in the P301L mice. To confirm that anti-tau antibodies could enter the brain and bind to pathological tau, FITC-tagged antibodies purified from a P301L mouse, with a high antibody titer against the immunogen, were injected into the carotid artery of P301L mice. These antibodies were subsequently detected within the brain and colocalized with PHF1 and MC1 antibodies that recognize pathological tau. Currently, no treatment is available for clearing tau aggregates. Our present findings may lead to a novel therapy targeting one of the major hallmarks of Alzheimer's disease and frontotemporal dementia.

Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. Publishing Authors By Initials

AA Asuni,A Boutajangout,D Quartermain,EM Sigurdsson,

For similar microtubule-associated proteins: tau proteins research abstracts see: microtubule-associated proteins: tau proteins research

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Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of neuroscience : the official journal

VOLUME: 27

Page Numbers: 9115-29

Journal Abbreviation: J. Neurosci.

ISSN: 1529-2401

DAY: 22

MONTH: Aug

YEAR: 2007

Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8102140

Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. Keywords Mesh Terms:

KEYWORDS: tau Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. Information

Substance Name: Leucine

Registry Number: 61-90-5

Grant and Affiliation Information for Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements.

AFFILIATION: Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA.

Country: United States

AGENCY: United States NIA

GRANT: AG5891

ACRONYM: AG

MEDLINETA: J Neurosci

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