A new study led by University of Texas Medical Branch at Galveston researchers revealed that targeting toxic tau oligomers with a specific immunotherapy also decreases beta-amyloid toxic protein aggregates, leading to improvements in cognitive decline in a mouse model of Alzheimer’s disease. The study, titled “Tau Immunotherapy Modulates Both Pathological Tau and Upstream Amyloid Pathology in an Alzheimer’s Disease Mouse Model” was published in The Journal of Neuroscience.
Alzheimer’s disease is a neurological disorder characterized by memory loss and cognitive impairment due to progressive death of neuron cells. Currently, Alzheimer’s is the sixth leading cause of death in the United States, according to data from the Centers for Disease Control and Prevention, while there are an estimated 36 million people worldwide diagnosed with Alzheimer’s or with a related dementia. Established causes for Alzheimer’s include the accumulation of beta-amyloid protein in brain cells’ plaques and the downstream triggering of tau protein aggregates, a toxic tau accumulation known as “tau oligomers.” However, how the accumulation of both beta-amyloid and tau protein results in memory loss is currently poorly understood.
The team targeted toxic tau oligomers via an immunotherapy strategy with oligomer-specific antibodies in a mouse model of Alzheimer’s disease. The authors observed that this immunotherapy was able to reduce the levels of tau oligomers and reversed memory decline. Surprisingly, authors noted the immunotherapy directed against tau oligomers also decreased the levels of amyloid beta oligomers, therefore suggesting a functional link between both proteins in promoting Alzheimer’s cognitive decline.
Based on these results, it seems targeting tau toxic protein with immunotherapy is a potential strategy to prevent progressive memory and cognitive decline in Alzheimer’s patients. Notably, the immunotherapy strategy targets only the toxic forms of tau protein leaving the normal tau proteins unharmed to perform their normal functions in the brain.
Rakez Kayed, associated professor in the Mitchell Center for Neurodegenerative Diseases, Department of Neurology at University of Texas Medical Branch, Galveston commented in a press release, “Our findings with this immunotherapy study indicate a link between tau oligomers and amyloid beta. Because of this relationship, removing tau oligomers with our immunotherapy may also decrease the harmful effects amyloid beta and mitigate memory deficits.”