{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:15:49Z","timestamp":1793376949190,"version":"4.5.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,10]]},"abstract":"<jats:p>\n                    Synapse loss correlates with a cognitive decline in Alzheimer's disease (AD), but whether this is caused by fibrillar deposits known as senile plaques or soluble oligomeric forms of amyloid \u03b2 (A\u03b2) is controversial. By using array tomography, a technique that combines ultrathin sectioning of tissue with immunofluorescence, allowing precise quantification of small structures, such as synapses, we have tested the hypothesis that oligomeric A\u03b2 surrounding plaques contributes to synapse loss in a mouse model of AD. We find that senile plaques are surrounded by a halo of oligomeric A\u03b2. Analysis of &gt;14,000 synapses (represented by PSD95-stained excitatory synapses) shows that there is a 60% loss of excitatory synapses in the halo of oligomeric A\u03b2 surrounding plaques and that the density increases to reach almost control levels in volumes further than 50 \u03bcm from a plaque in an approximately linear fashion (linear regression,\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.9;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). Further, in transgenic cortex, microdeposits of oligomeric A\u03b2 associate with a subset of excitatory synapses, which are significantly smaller than those not in contact with oligomeric A\u03b2. The proportion of excitatory synapses associated with A\u03b2 correlates with decreasing density (correlation, \u22120.588;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). These data show that senile plaques are a potential reservoir of oligomeric A\u03b2, which colocalizes with the postsynaptic density and is associated with spine collapse, reconciling the apparently competing schools of thought of \u201cplaque\u201d vs. \u201coligomeric A\u03b2\u201d as the synaptotoxic species in the brain of AD patients.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0811698106","type":"journal-article","created":{"date-parts":[[2009,2,19]],"date-time":"2009-02-19T21:39:48Z","timestamp":1235079588000},"page":"4012-4017","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":792,"title":["Oligomeric amyloid \u03b2 associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques"],"prefix":"10.1073","volume":"106","author":[{"given":"Robert M.","family":"Koffie","sequence":"first","affiliation":[{"name":"Neurology Department, Massachusetts General Hospital, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Meyer-Luehmann","sequence":"additional","affiliation":[{"name":"Neurology Department, Massachusetts General Hospital, Charlestown, MA 02129;"},{"name":"Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Ludwig-Maximilians-University, 80336 Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadafumi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Neurology Department, Massachusetts General Hospital, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Adams","sequence":"additional","affiliation":[{"name":"Neurology Department, Massachusetts General Hospital, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Mielke","sequence":"additional","affiliation":[{"name":"Neurology Department, Massachusetts General Hospital, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Garcia-Alloza","sequence":"additional","affiliation":[{"name":"Neurology Department, Massachusetts General Hospital, Charlestown, MA 02129;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina D.","family":"Micheva","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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