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For the present study, our objective was to analyze the age-dependent morphological and architectural changes of the cerebral vasculature of APP23 tg mice. To visualize the 3D arrangement of the entire brain vasculature, we used vascular corrosion casts. Already at young ages, when typically parenchymal amyloid plaques are not yet present, APP23 tg mice had significant alterations, particularly of the microvasculature, often accompanied by small deposits attached to the vessels. In older animals, vasculature abruptly ended at amyloid plaques, resulting in holes. Often, small deposits were sitting near or at the end of truncated vessels. Between such holes, the surrounding vascular array appeared more dense and showed features typical for angiogenesis. We propose that small amyloid aggregates associated with the microvasculature lead to morphological and architectural alterations of the vasculature, resulting in altered local blood flow. The characteristic early onset of vascular alterations suggests that imaging blood flow and\/or vasculature architecture could be used as a tool for early diagnosis of the disease and to monitor therapies.<\/jats:p>","DOI":"10.1073\/pnas.0709788105","type":"journal-article","created":{"date-parts":[[2008,2,27]],"date-time":"2008-02-27T21:37:26Z","timestamp":1204148246000},"page":"3587-3592","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":231,"title":["Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease"],"prefix":"10.1073","volume":"105","author":[{"given":"Eric P.","family":"Meyer","sequence":"first","affiliation":[{"name":"*Department of Zoology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Ulmann-Schuler","sequence":"additional","affiliation":[{"name":"*Department of Zoology, University of Z\u00fcrich, Winterthurerstrasse 190, CH-8057 Z\u00fcrich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Staufenbiel","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Basel, Nervous System Research, CH-4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Krucker","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Inc., Discovery Technologies, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,3,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1991.tb00666.x"},{"key":"e_1_3_3_3_2","volume-title":"Alzheimer Disease","author":"Terry RD","year":"1994","unstructured":"RD Terry, KR, KL Bick, SS Sisodia Alzheimer Disease (Raven, New York, 1994)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000191298.68045.50"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00119-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000143317.70478.b3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00137-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1387"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2005.04.017"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1993.11740127"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-24-08453.2003"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-16-07218.2002"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/5715"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.17.9735"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00022.2002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1287"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:AGEN.0000037335.17717.bf"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(04)00683-0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.14088"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13287"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20263"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/sca.4950100202"},{"key":"e_1_3_3_23_2","first-page":"435","article-title":"Scanning electron microscopy of plastic corrosion casts: The morphological distinction of arteries and veins.","author":"Miodonski AJ","year":"1976","unstructured":"AJ Miodonski, KC Hodde, C Bakker, Scanning electron microscopy of plastic corrosion casts: The morphological distinction of arteries and veins. 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