HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model.

Abstract
Harnessing the immune system to clear protein aggregates is emerging as a promising approach to treat various neurodegenerative diseases. In Alzheimer's disease (AD), several clinical trials are ongoing using active and passive immunotherapy targeting the amyloid-β (Aβ) peptide. Limited emphasis has been put into clearing tau/tangle pathology, another major hallmark of the disease. Recent findings from the first Aβ vaccination trial suggest that this approach has limited effect on tau pathology and that Aβ plaque clearance may not halt or slow the progression of dementia in individuals with mild-to-moderate AD. To assess within a reasonable timeframe whether targeting tau pathology with immunotherapy could prevent cognitive decline, we developed a new model with accelerated tangle development. It was generated by crossing available strains that express all six human tau isoforms and the M146L presenilin mutation. Here, we show that this unique approach completely prevents severe cognitive impairment in three different tests. This remarkable effect correlated well with extensive clearance of abnormal tau within the brain. Overall, our findings indicate that immunotherapy targeting pathological tau is very feasible for tauopathies, and should be assessed in clinical trials in the near future.
AuthorsAllal Boutajangout, David Quartermain, Einar M Sigurdsson
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 30 Issue 49 Pg. 16559-66 (Dec 08 2010) ISSN: 1529-2401 [Electronic] United States
PMID21147995 (Publication Type: Journal Article)
Chemical References
  • Amyloid beta-Peptides
  • Antibodies
  • DNA-Binding Proteins
  • PSEN1 protein, human
  • Peptide Fragments
  • Phf1 protein, mouse
  • Polycomb-Group Proteins
  • Presenilin-1
  • Transcription Factors
  • amyloid beta-protein (1-42)
  • tau Proteins
Topics
  • Alzheimer Disease (blood, complications, genetics, immunology)
  • Amyloid beta-Peptides (genetics, metabolism)
  • Animals
  • Antibodies (blood, therapeutic use)
  • Behavior, Animal (physiology)
  • Brain (metabolism, pathology)
  • Cognition Disorders (etiology, immunology, therapy)
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay (methods)
  • Female
  • Gliosis (etiology)
  • Humans
  • Immunotherapy (methods)
  • Male
  • Maze Learning (physiology)
  • Memory Disorders (etiology, immunology)
  • Mice
  • Mice, Transgenic
  • Motor Activity (genetics, immunology)
  • Mutation (genetics, immunology)
  • Peptide Fragments (genetics, metabolism)
  • Polycomb-Group Proteins
  • Presenilin-1 (genetics)
  • Psychomotor Performance (drug effects)
  • Recognition, Psychology (physiology)
  • Rotarod Performance Test
  • Statistics, Nonparametric
  • Transcription Factors (metabolism)
  • tau Proteins (genetics, immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: