{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:54:19Z","timestamp":1789116859575,"version":"build-2803163510"},"reference-count":142,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Spanish \u201cMinisterio de Ciencia e Innovaci\u00f3n\u201d","doi-asserted-by":"crossref","award":["PGC2018-094307-B-I00"],"award-info":[{"award-number":["PGC2018-094307-B-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED","award":["CB06\/05\/0066"],"award-info":[{"award-number":["CB06\/05\/0066"]}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","award":["ZEN-15-321663"],"award-info":[{"award-number":["ZEN-15-321663"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Universidad Nacional de Educaci\u00f3n a Distancia (UNED","award":["2014-040-UNED-POST"],"award-info":[{"award-number":["2014-040-UNED-POST"]}]},{"name":"Spanish \u201cMinisterio de Educaci\u00f3n, Cultura y Deporte","award":["FPU14\/02245"],"award-info":[{"award-number":["FPU14\/02245"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer\u2019s disease is the most common form of dementia, characterized by a persistent and progressive impairment of cognitive functions. Alzheimer\u2019s disease is typically associated with extracellular deposits of amyloid-\u03b2 peptide and accumulation of abnormally phosphorylated tau protein inside neurons (amyloid-\u03b2 and neurofibrillary pathologies). It has been proposed that these pathologies cause neuronal degeneration and synaptic alterations, which are thought to constitute the major neurobiological basis of cognitive dysfunction in Alzheimer\u2019s disease. The hippocampal formation is especially vulnerable in the early stages of Alzheimer\u2019s disease. However, the vast majority of electron microscopy studies have been performed in animal models. In the present study, we performed an extensive 3D study of the neuropil to investigate the synaptic organization in the stratum pyramidale and radiatum in the CA1 field of Alzheimer\u2019s disease cases with different stages of the disease, using focused ion beam\/scanning electron microscopy (FIB\/SEM). In cases with early stages of Alzheimer\u2019s disease, the synapse morphology looks normal and we observed no significant differences between control and Alzheimer\u2019s disease cases regarding the synaptic density, the ratio of excitatory and inhibitory synapses, or the spatial distribution of synapses. However, differences in the distribution of postsynaptic targets and synaptic shapes were found. Furthermore, a lower proportion of larger excitatory synapses in both strata were found in Alzheimer\u2019s disease cases. Individuals in late stages of the disease suffered the most severe synaptic alterations, including a decrease in synaptic density and morphological alterations of the remaining synapses. Since Alzheimer\u2019s disease cases show cortical atrophy, our data indicate a reduction in the total number (but not the density) of synapses at early stages of the disease, with this reduction being much more accentuated in subjects with late stages of Alzheimer\u2019s disease. The observed synaptic alterations may represent a structural basis for the progressive learning and memory dysfunctions seen in Alzheimer\u2019s disease cases.<\/jats:p>","DOI":"10.1093\/brain\/awaa406","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T15:12:45Z","timestamp":1604675565000},"page":"553-573","source":"Crossref","is-referenced-by-count":81,"title":["Three-dimensional analysis of synaptic organization in the hippocampal CA1\u00a0field in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7895-5961","authenticated-orcid":false,"given":"Marta","family":"Montero-Crespo","sequence":"first","affiliation":[{"name":"Instituto Cajal, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Av. Doctor Arce, 37, 28002 Madrid, Spain"},{"name":"Laboratorio Cajal de Circuitos Corticales, Centro de Tecnolog\u00eda Biom\u00e9dica, Universidad Polit\u00e9cnica de Madrid, 28223 Pozuelo de Alarc\u00f3n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-5971","authenticated-orcid":false,"given":"Marta","family":"Dom\u00ednguez-\u00c1lvaro","sequence":"additional","affiliation":[{"name":"Laboratorio Cajal de Circuitos Corticales, Centro de Tecnolog\u00eda Biom\u00e9dica, Universidad Polit\u00e9cnica de Madrid, 28223 Pozuelo de Alarc\u00f3n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2649-7097","authenticated-orcid":false,"given":"Lidia","family":"Alonso-Nanclares","sequence":"additional","affiliation":[{"name":"Instituto Cajal, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Av. Doctor Arce, 37, 28002 Madrid, Spain"},{"name":"Laboratorio Cajal de Circuitos Corticales, Centro de Tecnolog\u00eda Biom\u00e9dica, Universidad Polit\u00e9cnica de Madrid, 28223 Pozuelo de Alarc\u00f3n, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, c\/Valderrebollo, 5, 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-0660","authenticated-orcid":false,"given":"Javier","family":"DeFelipe","sequence":"additional","affiliation":[{"name":"Instituto Cajal, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Av. Doctor Arce, 37, 28002 Madrid, Spain"},{"name":"Laboratorio Cajal de Circuitos Corticales, Centro de Tecnolog\u00eda Biom\u00e9dica, Universidad Polit\u00e9cnica de Madrid, 28223 Pozuelo de Alarc\u00f3n, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, c\/Valderrebollo, 5, 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4865-8974","authenticated-orcid":false,"given":"Lidia","family":"Blazquez-Llorca","sequence":"additional","affiliation":[{"name":"Laboratorio Cajal de Circuitos Corticales, Centro de Tecnolog\u00eda Biom\u00e9dica, Universidad Polit\u00e9cnica de Madrid, 28223 Pozuelo de Alarc\u00f3n, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, c\/Valderrebollo, 5, 28031 Madrid, Spain"},{"name":"Departamento de Psicobiolog\u00eda, Facultad de Psicolog\u00eda, Universidad Nacional de Educaci\u00f3n a Distancia (UNED), c\/Juan del Rosal, 10, 28040 Madrid, Spain"},{"name":"Secci\u00f3n Departamental de Anatom\u00eda y Embriolog\u00eda (Veterinaria), Facultad de Veterinaria, Universidad Complutense de Madrid, Av. 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