{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:36:47Z","timestamp":1770741407034,"version":"3.49.0"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Aggregation and deposition of amyloid-\u03b2 (A\u03b2) peptides in extracellular plaques and in the cerebral vasculature are prominent neuropathological features of Alzheimer\u2019s disease (AD) and closely associated with the pathogenesis of AD. Amyloid plaques in the brains of most AD patients and transgenic mouse models exhibit heterogeneity in the composition of A\u03b2 deposits, due to the occurrence of elongated, truncated, and post-translationally modified A\u03b2 peptides. Importantly, changes in the deposition of these different A\u03b2 variants are associated with the clinical disease progression and considered to mark sequential phases of plaque and cerebral amyloid angiopathy (CAA) maturation at distinct stages of AD. We recently showed that A\u03b2 phosphorylated at serine residue 26 (pSer26A\u03b2) has peculiar characteristics in aggregation, deposition, and neurotoxicity. In the current study, we developed and thoroughly validated novel monoclonal and polyclonal antibodies that recognize A\u03b2 depending on the phosphorylation-state of Ser26. Our results demonstrate that selected phosphorylation state-specific antibodies were able to recognize Ser26 phosphorylated and non-phosphorylated A\u03b2 with high specificity in enzyme-linked immunosorbent assay (ELISA) and Western Blotting (WB) assays. Furthermore, immunofluorescence analyses with these antibodies demonstrated the occurrence of pSer26A\u03b2 in transgenic mouse brains that show differential deposition as compared to non-phosphorylated A\u03b2 (npA\u03b2) or other modified A\u03b2 species. Notably, pSer26A\u03b2 species were faintly detected in extracellular A\u03b2 plaques but most prominently found intraneuronally and in cerebral blood vessels. In conclusion, we developed new antibodies to specifically differentiate A\u03b2 peptides depending on the phosphorylation state of Ser26, which are applicable in ELISA, WB, and immunofluorescence staining of mouse brain tissues. These site- and phosphorylation state-specific A\u03b2 antibodies represent novel tools to examine phosphorylated A\u03b2 species to further understand and dissect the complexity in the age-related and spatio-temporal deposition of different A\u03b2 variants in transgenic mouse models and human AD brains.<\/jats:p>","DOI":"10.3389\/fnmol.2020.619639","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T05:53:28Z","timestamp":1610690008000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Novel Phosphorylation-State Specific Antibodies Reveal Differential Deposition of Ser26 Phosphorylated A\u03b2 Species in a Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Sathish","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshay","family":"Kapadia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Theil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranav","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Riffel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Heneka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Walter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/alz.12068","article-title":"2020 Alzheimer\u2019s disease facts and figures","volume":"16","year":"2020","journal-title":"Alzheimers Dement."},{"key":"B2","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/nan.12212","article-title":"Investigation of A\u03b2 phosphorylated at serine 8 (pA\u03b2) in Alzheimer\u2019s disease, dementia with lewy bodies and vascular dementia","volume":"41","author":"Ashby","year":"2015","journal-title":"Neuropathol. 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