Spread of tau down neural circuits precedes synapse and neuronal loss in the rTgTauEC mouse model of early Alzheimer’s disease - Data from 2017 Publication

This is the raw data associated with the manuscript Pickett et al (2017) Synapse. We provide the raw images and analysis files. Due to University of Edinburgh DataShare space constraints, we cannot upload the processed images but can share them upon request (email [email protected]). # Paper abstract: # Synaptic dysfunction and loss is the strongest pathological correlate of cognitive decline in Alzheimer’s disease (AD) with increasing evidence implicating neuropathological tau protein in this process. Despite the knowledge that tau spreads through defined synaptic circuits, it is currently unknown whether synapse loss occurs before the accumulation of tau or as a consequence. To address this, we have used array tomography to examine an rTgTauEC mouse model expressing a P301L human tau transgene and a transgene labelling cytoplasm red (tdTomato) and presynaptic terminals green (Synaptophysin-EGFP). All transgenes are restricted primarily to the entorhinal cortex using the neuropsin promotor to drive tTA expression. It has previously been shown that rTgTauEC mice exhibit neuronal loss in the entorhinal cortex and synapse density loss in the middle molecular layer (MML) of the dentate gyrus at 24 months of age. Here we observed the density of tau-expressing and total pre synapses, and the spread of tau into the postsynapse in the MML of 3-6, 9 and 18 months old red-green-rTgTauEC mice. We observe no loss of synapse density in the MML up to 18 months even in axons expressing tau. Despite the maintenance of synapse density, we see spread of human tau from presynaptic terminals to postsynaptic compartments in the MML at very early ages, indicating that the spread of tau through neural circuits is not due to the degeneration of axon terminals and is an early feature of the disease process.

Spires-Jones, Tara; Pickett, Eleanor. (2017). Spread of tau down neural circuits precedes synapse and neuronal loss in the rTgTauEC mouse model of early Alzheimer’s disease - Data from 2017 Publication, [dataset]. University of Edinburgh. http://dx.doi.org/10.7488/ds/1706.