{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:02:43Z","timestamp":1791489763036,"version":"4.3.4"},"reference-count":88,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T00:00:00Z","timestamp":1361318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2013,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Synapse loss, rather than the hallmark amyloid\u2010\u03b2 (A\u03b2) plaques or tau\u2010filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer's disease (AD) brain. The role of A\u03b2 in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau overexpression in a mouse model (rTg4510) will lead to age\u2010dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold\u2010based counting and a manual stereology\u2010based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multiphoton in vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons, suggesting these cells may be particularly vulnerable to tau\u2010induced degeneration. Postmortem, we confirm the presence of tau in dendritic spines of rTg4510\u2010YFP mouse brain by array tomography. These data implicate tau\u2010induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes, thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together, these data show morphological and biochemical synaptic consequences in response to tau overexpression in the rTg4510 mouse model. J. Comp. Neurol., 521:1334\u20131353, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.23234","type":"journal-article","created":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T03:52:32Z","timestamp":1349841152000},"page":"1334-1353","source":"Crossref","is-referenced-by-count":117,"title":["Synaptic alterations in the rTg4510 mouse model of tauopathy"],"prefix":"10.1002","volume":"521","author":[{"given":"Katherine J.","family":"Kopeikina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Polydoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwan\u2010Ching","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Yaeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George 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