FIGURE 4.

Trans‐synaptic trafficking of pT217‐tau in aging rhesus macaques. Early‐stage, soluble pT217‐tau propagates between excitatory neurons within glutamate‐like synapses in “early” aged (18–24 years) macaque ERC layer II (A‐B) and in “late” aged (26–31 years) macaque dlPFC layer III (C‐D). Trans‐synaptic propagation of pT217‐tau occurs via omega‐shaped endosome‐like vesicular profiles on the plasma membrane within dendritic spines, specifically within the synapse (insets). All dendritic spines receive axospinous Type I asymmetric glutamatergic‐like synapses. Red arrowheads point to pT217‐tau immunoreactivity. Black arrows point to the synapse; white arrowheads indicate an omega‐shaped profile on the plasma membrane. The SER is pseudocolored in pink. Profiles are pseudocolored for clarity. Scale bars, 200 nm. Ax, axon; dlPFC, dorsolateral prefrontal cortex; ERC, entorhinal cortex; Mit, mitochondria; pT217‐tau, tau phosphorylated at threonine‐217; SER, smooth endoplasmic reticulum; Sp, dendritic spine