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Human tau increases amyloid β plaque size but not amyloid β‐mediated synapse loss in a novel mouse model of Alzheimer's disease
Author(s) -
Jackson Rosemary J.,
Rudinskiy Nikita,
Herrmann Abigail G.,
Croft Shaun,
Kim JeeSoo Monica,
Petrova Veselina,
RamosRodriguez Juan Jose,
Pitstick Rose,
Wegmann Susanne,
GarciaAlloza Monica,
Carlson George A.,
Hyman Bradley T.,
SpiresJones Tara L.
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13442
Subject(s) - synapse , senile plaques , neurite , presenilin , genetically modified mouse , neuroscience , amyloid (mycology) , biology , alzheimer's disease , microbiology and biotechnology , chemistry , pathology , transgene , medicine , disease , genetics , gene , in vitro
Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP / PS 1/ rT g21221 line, by crossing APP / PS 1 mice, which develop Aβ‐plaques and synapse loss, with rT g21221 mice, which overexpress wild‐type human tau. When compared to the APP / PS 1 mice without human tau, the cross‐sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque‐associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild‐type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque‐associated synapse loss.