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Nevertheless, its distribution and clearance before A\u03b2 plaque formation needs to be elucidated. Using an optimized immunofluorescent staining method, we examined the distribution of A\u03b2 in the post-mortem parietal cortex of 35 subjects, 30 to 65 years of age,\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b53\/\u03b53, without AD lesions. We used 11A1, an antibody against an A\u03b2 conformer which forms neurotoxic oligomers. 11A1 immunoreactivity (IR) was present in cortical neurons, pericapillary spaces, astrocytes and the extracellular compartment at 30 years of age. The percentage of neurons with 11A1 IR did not change with age, but the number and percentage of astrocytes with 11A1 IR gradually increased. Notably, the percentage of pericapillary spaces labeled with 11A1 IR declined significantly in the 5\n                    <jats:sup>th<\/jats:sup>\n                    decade of the life, at the same time that 11A1 IR increased in the extracellular space. Our findings indicate that the A\u03b2 toxic conformer is normally present in various cell types and brain parenchyma, and appears to be constitutively produced, degraded, and cleared from the inferior parietal cortex. The decrease in pericapillary A\u03b2 and the concomitant increase of extracellular A\u03b2 may reflect an age-associated impairment in A\u03b2 clearance from the brain.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-35004-3","type":"journal-article","created":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T10:18:20Z","timestamp":1541758700000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Amyloid \u03b2 toxic conformer has dynamic localization in the human inferior parietal cortex in absence of amyloid plaques"],"prefix":"10.1038","volume":"8","author":[{"given":"Yusuke","family":"Kageyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Pletnikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gay L.","family":"Rudow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Irie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7109-8568","authenticated-orcid":false,"given":"Kazuhiro","family":"Irie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Resnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee J.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Troncoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,15]]},"reference":[{"key":"35004_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1056\/NEJMra0909142","volume":"362","author":"HW Querfurth","year":"2010","unstructured":"Querfurth, H. 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