Tau Seeding of Neurons Negatively Affects Neuronal Function
Key findings
- Tau protein, which accumulates in multiple neurodegenerative diseases, has been shown in animal models to have the ability to spread throughout the brain. The concept is that aggregates of tau form "seeds" that propagate to other neurons.
Tau protein, which accumulates in multiple neurodegenerative diseases, has been shown in animal models to have the ability to spread throughout the brain. The concept is that aggregates of tau form "seeds" that propagate to other neurons.
Massachusetts General Hospital's Marta Perez-Rando, PhD, postdoctoral researcher, and Bradley T. Hyman, MD, PhD, director of the Alzheimer's Disease Research Unit at the MassGeneral Institute for Neurodegenerative Disease (MIND), and colleagues have become the first to investigate how these recipient neurons respond to tau uptake. In Acta Neuropathologica Communications, they noted changes in synaptic and metabolic pathways that were similar to changes previously observed in human Alzheimer's disease (AD).
Study Methods
The study made use of rTg4510 transgenic mice. These mice overexpress human tau with the P301L mutation and develop tau aggregates in cortical and hippocampal neurons as they age.
Using RNAScope—high-resolution, multicolor in situ hybridization technology—the team examined the brains of rTg4510 mice that were young (4–6 months of age) or old (12 months of age).
Identification of Recipient Neurons
As expected, RNAScope permitted identification of individual neurons that both overexpressed the human tau transgene and developed tau-positive inclusions. However, a smaller subpopulation of neurons in the cortex developed tau-positive inclusions even though they did not express the transgene—a demonstration of tau seeding. The latter were termed recipient neurons.