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Published on: May 28, 2017
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice
Cristian A Lasagna-Reeves1, Diana L Castillo-Carranza, Urmi Sengupta
1George P, and Cynthia Woods Mitchell Center for Neurodegenerative Diseases, Departments of Neurology, and Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555-1045, USA. rakayed@utmb.edu.
Tau oligomers, a toxic form of tau protein, are neurotoxic in vivo and impair memory. Targeting these tau oligomers may offer new therapeutic strategies for Alzheimer's disease and other tauopathies.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- The role of tau protein aggregates in Alzheimer's disease (AD) progression is debated.
- Emerging evidence suggests tau oligomers, a pre-filamentous form, may be the most toxic tau species.
Purpose of the Study:
- To investigate the in vivo neurotoxicity of recombinant human tau oligomers.
- To determine the effects of tau oligomers on cognitive function, synaptic integrity, and mitochondrial function.
Main Methods:
- Subcortical stereotaxic injection of recombinant full-length human tau protein (oligomers, fibrils, monomers) into mice.
- Assessment of memory consolidation, synaptic protein levels, mitochondrial function, and apoptotic pathways.
Main Results:
- Tau oligomers, but not fibrils or monomers, significantly impaired memory consolidation in vivo.
- Tau oligomers reduced synaptic vesicle-associated proteins (synaptophysin, septin-11), indicating synaptic dysfunction.
- Tau oligomers induced mitochondrial dysfunction by decreasing electron transport chain complex I and activated caspase-9.
Conclusions:
- Tau oligomers represent an acutely toxic tau species in vivo.
- Tau oligomers induce neurodegeneration by disrupting mitochondrial and synaptic function, key early features of AD and tauopathies.
- Targeting tau oligomers presents a promising therapeutic strategy for tauopathies.
