{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:22:25Z","timestamp":1789424545387,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T00:00:00Z","timestamp":1431475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000883","name":"University of Bristol","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000883","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["1477\/6"],"award-info":[{"award-number":["1477\/6"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Alzheimer Foundation","award":["12854"],"award-info":[{"award-number":["12854"]}]},{"name":"Sigmund Gestetner Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Aims<\/jats:title>Deposition of amyloid beta (A<\/jats:styled-content>\u03b2) in the brain is one of the defining abnormalities of A<\/jats:styled-content>lzheimer's disease (AD<\/jats:styled-content>). Phosphorylation of A<\/jats:styled-content>\u03b2 at serine 8 (pA<\/jats:styled-content>\u03b2) has been implicated in its aggregation in vitro and pA<\/jats:styled-content>\u03b2 level has been shown to be significantly elevated in AD<\/jats:styled-content>. We aimed to assess the specificity of pA<\/jats:styled-content>\u03b2 for AD<\/jats:styled-content> and have investigated associations of pA<\/jats:styled-content>\u03b2 with parenchymal and cerebrovascular accumulation of A<\/jats:styled-content>\u03b2, disease progression, angiotensin\u2010converting enzyme activity and APOE<\/jats:italic><\/jats:styled-content> genotype.<\/jats:p><\/jats:sec>Methods<\/jats:title>The distribution of pA<\/jats:styled-content>\u03b2 was studied by immunohistochemistry in sporadic and familial AD<\/jats:styled-content>, pure dementia with L<\/jats:styled-content>ewy bodies (DLB<\/jats:styled-content>), pure vascular dementia (VaD<\/jats:styled-content>) and age\u2010matched controls. Soluble and insoluble (guanidine\u2010extractable) pA<\/jats:styled-content>\u03b2 level was measured by enzyme\u2010linked immunosorbent assay (ELISA<\/jats:styled-content>) in the midfrontal and parahippocampal cortex in sporadic AD<\/jats:styled-content> (n<\/jats:italic>\u2009=\u200920, 10 with B<\/jats:styled-content>raak tangle stages of III<\/jats:styled-content>\u2013IV<\/jats:styled-content> and 10 of stages V<\/jats:styled-content>\u2013VI<\/jats:styled-content>), DLB<\/jats:styled-content> (n<\/jats:italic>\u2009=\u200910), VaD<\/jats:styled-content> (n<\/jats:italic>\u2009=\u200910) and age\u2010matched controls (n<\/jats:italic>\u2009=\u200920).<\/jats:p><\/jats:sec>Results<\/jats:title>We found pA<\/jats:styled-content>\u03b2 to be associated with only a subset of A<\/jats:styled-content>\u03b2 plaques and vascular deposits in sporadic and familial AD<\/jats:styled-content>, with absent or minimal immunohistochemically detectable pA<\/jats:styled-content>\u03b2 in control, DLB<\/jats:styled-content> and VaD<\/jats:styled-content> brains. In both brain regions, insoluble pA<\/jats:styled-content>\u03b2 level was significantly elevated only in advanced AD<\/jats:styled-content> (B<\/jats:styled-content>raak tangle stage of V<\/jats:styled-content> or VI<\/jats:styled-content>) and in the parahippocampus soluble and insoluble pA<\/jats:styled-content>\u03b2 level increased with the number of APOE<\/jats:italic><\/jats:styled-content> \u03b54 alleles.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>These results indicate that pA<\/jats:styled-content>\u03b2 accumulation in the parenchyma and vasculature is largely restricted to late\u2010stage AD<\/jats:styled-content> (B<\/jats:styled-content>raak tangle stage V<\/jats:styled-content>\u2013VI<\/jats:styled-content>).<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12212","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T09:56:28Z","timestamp":1419933388000},"page":"428-444","source":"Crossref","is-referenced-by-count":27,"title":["Investigation of A<\/scp>\u03b2 phosphorylated at serine 8 (pA<\/scp>\u03b2) in A<\/scp>lzheimer's disease, dementia with L<\/scp>ewy bodies and vascular dementia"],"prefix":"10.1111","volume":"41","author":[{"given":"Emma L.","family":"Ashby","sequence":"first","affiliation":[{"name":"Dementia Research Group Institute of Clinical Neurosciences School of Clinical Sciences University of Bristol, Level 1 Learning and Research, Southmead Hospital Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Miners","sequence":"additional","affiliation":[{"name":"Dementia Research Group Institute of Clinical Neurosciences School of Clinical Sciences University of Bristol, Level 1 Learning and Research, Southmead Hospital Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Love","sequence":"additional","affiliation":[{"name":"Dementia Research Group Institute of Clinical Neurosciences School of Clinical Sciences University of Bristol, Level 1 Learning and Research, Southmead Hospital Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick G.","family":"Kehoe","sequence":"additional","affiliation":[{"name":"Dementia Research Group Institute of Clinical Neurosciences School of Clinical Sciences University of Bristol, Level 1 Learning and Research, Southmead Hospital Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61349-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.17.11914"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb23043.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201750200"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100362"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.138"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1107-8"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt362"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.279133"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0910-3"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.1.190"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200308060-00027"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2990.2003.00457.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.09.002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00374.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-101395"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.10.6641"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-120658"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.12.2025"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu040"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12130"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt257"},{"key":"e_1_2_6_25_1","first-page":"163","article-title":"Angiotensin\u2010converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes","volume":"1","author":"Miners S","year":"2009","journal-title":"Am J Transl Res"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10498"},{"key":"e_1_2_6_27_1","first-page":"73","article-title":"ACE variants and association with brain Abeta levels in Alzheimer's disease","volume":"3","author":"Miners JS","year":"2010","journal-title":"Am J Transl Res"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101326\u20108\u201016"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9649"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4315-03.2004"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408127200"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64963-2"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnan.12212","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nan.12212","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T19:34:49Z","timestamp":1696188889000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nan.12212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,13]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1111\/nan.12212"],"URL":"https:\/\/doi.org\/10.1111\/nan.12212","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,13]]}}}