Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model

Abstract

Many potential treatments for Alzheimer's disease target amyloid-β peptides (Aβ), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Aβ-induced cognitive impairments. Here, we found that reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Aβ levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Aβ- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions.

Keywords

Genetically modified mouseEndogenyExcitotoxicityAlzheimer's diseaseNeuroscienceTransgeneAmyloid (mycology)DiseaseAmyloid precursor proteinTau proteinBACE1-ASMedicineBiologyEndocrinologyInternal medicineReceptorPathologyBiochemistryGlutamate receptorGene

Affiliated Institutions

Related Publications

Amyloid-β/Fyn–Induced Synaptic, Network, and Cognitive Impairments Depend on Tau Levels in Multiple Mouse Models of Alzheimer's Disease

Erik D. Roberson , Brian Halabisky , Jong W. Yoo +10 more

Alzheimer's disease (AD), the most common neurodegenerative disorder, is a growing public health problem and still lacks effective treatments. Recent evidence suggests that micr...

2011 Journal of Neuroscience 634 citations

Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP

Jada Lewis , Dennis W. Dickson , Wen-Lang Lin +11 more

JNPL3 transgenic mice expressing a mutant tau protein, which develop neurofibrillary tangles and progressive motor disturbance, were crossed with Tg2576 transgenic mice expressi...

2001 Science 1569 citations

Induction of Tau Pathology by Intracerebral Infusion of Amyloid-β-Containing Brain Extract and by Amyloid-β Deposition in APP × Tau Transgenic Mice

Tristan Bolmont , Florence Clavaguera , Melanie Meyer‐Luehmann +7 more

Alzheimer's disease presents morphologically with senile plaques, primarily made of extracellular amyloid-beta (A beta) deposits, and neurofibrillary lesions, which consist of i...

2007 American Journal Of Pathology 261 citations

Tau is essential to β-amyloid-induced neurotoxicity

Mark Rapoport , Hana N. Dawson , Lester I. Binder +2 more

Senile plaques and neurofibrillary tangles, the two hallmark lesions of Alzheimer's disease, are the results of the pathological deposition of proteins normally present througho...

2002 Proceedings of the National Academy o... 793 citations

Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L)

Martin Ramsden , Linda Kotilinek , Colleen L. Forster +9 more

Here, we describe the generation of a novel transgenic mouse model of human tauopathy. The rTg(tau P301L )4510 mouse expresses the P301L mutation in tau (4R0N) associated with f...

2005 Journal of Neuroscience 705 citations

Publication Info

Year: 2007
Type: article
Volume: 316
Issue: 5825
Pages: 750-754
Citations: 1837
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1837

OpenAlex

Cite This

APA Style

                            
                                
                                    Erik D. Roberson, 
                                
                                    Kimberly Scearce‐Levie, 
                                
                                    Jorge J. Palop
                                
                                et al.
                            
                            (2007). 
                            Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model. 
                            Science
                            , 316
                            (5825)
                            , 750-754.
                            https://doi.org/10.1126/science.1141736
                        

Identifiers

DOI: 10.1126/science.1141736