Synaptic distributions of pS214-tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline

Johanna L. Crimins, Rishi Puri, Katina C. Calakos, Frank Yuk, William G.M. Janssen, Yuko Hara, Peter R. Rapp, John H. Morrison

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Female rhesus monkeys and women are subject to age- and menopause-related deficits in working memory, an executive function mediated by the dorsolateral prefrontal cortex (dlPFC). Long-term cyclic administration of 17β-estradiol improves working memory, and restores highly plastic axospinous synapses within layer III dlPFC of aged ovariectomized monkeys. In this study, we tested the hypothesis that synaptic distributions of tau protein phosphorylated at serine 214 (pS214-tau) are altered with age or estradiol treatment, and couple to working memory performance. First, ovariectormized young and aged monkeys received vehicle or estradiol treatment, and were tested on the delayed response (DR) test of working memory. Serial section electron microscopic immunocytochemistry was then performed to quantitatively assess the subcellular synaptic distributions of pS214-tau. Overall, the majority of synapses contained pS214-tau immunogold particles, which were predominantly localized to the cytoplasm of axon terminals. pS214-tau was also abundant within synaptic and cytoplasmic domains of dendritic spines. The density of pS214-tau immunogold within the active zone, cytoplasmic, and plasmalemmal domains of axon terminals, and subjacent to the postsynaptic density within the subsynaptic domains of dendritic spines, were each reduced with age. None of the variables examined were directly linked to cognitive status, but a high density of pS214-tau immunogold particles within presynaptic cytoplasmic and plasmalemmal domains, and within postsynaptic subsynaptic and plasmalemmal domains, accompanied high synapse density. Together, these data support a possible physiological, rather than pathological, role for pS214-tau in the modulation of synaptic morphology in monkey dlPFC.

Original languageEnglish
Pages (from-to)856-873
Number of pages18
JournalJournal of Comparative Neurology
Issue number4
StatePublished - 1 Mar 2019


  • RRID:AB_2716719
  • RRID:AB_2750560
  • RRID:SCR_002865
  • RRID:SCR_014199
  • aging
  • area 46
  • delayed response
  • estradiol
  • menopause
  • pS214


Dive into the research topics of 'Synaptic distributions of pS214-tau in rhesus monkey prefrontal cortex are associated with spine density, but not with cognitive decline'. Together they form a unique fingerprint.

Cite this