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The AP\u20102 \u03b1\u2010adaptin subunit has two major isoforms, encoded by two separate genes:\n                      <jats:italic>AP2A1<\/jats:italic>\n                      and\n                      <jats:italic>AP2A2<\/jats:italic>\n                      . Endocytosis has been implicated in the pathogenesis of neurodegenerative disease, and recent studies linked \u03b1\u2010adaptins (gene variants, splicing defects and altered expression) with late\u2010onset Alzheimer's disease (LOAD) risk. Here, we used multiple antibodies to investigate \u03b1\u2010adaptin isoforms and their localization in human brains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The specificities of 10 different \u03b1\u2010adaptin antibodies were evaluated using immunoblots after human\n                      <jats:italic>AP2A1<\/jats:italic>\n                      and\n                      <jats:italic>AP2A2<\/jats:italic>\n                      plasmid transfection in cultured cells. Additional immunoblot analyses were then performed on protein homogenates from control and LOAD subjects. Formalin\u2010fixed, paraffin\u2010embedded brain sections from control and LOAD subjects were immunohistochemically stained, and immunofluorescence experiments were performed for quantitation of colocalisation with digital image analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight of the 10 evaluated antibodies recognised transfected \u03b1\u2010adaptin proteins on immunoblots. The \u03b1\u2010adaptin subspecies were relatively uniformly expressed in five different human brain regions. The \u03b1\u2010adaptins were present in the detergent\u2010insoluble fraction from cognitively impaired, but less so in control, brains. Immunohistochemical analyses showed colocalisation of AP2A1 with tau pathology in LOAD brains. By contrast, AP2A2 colocalised with microglial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These observations provide evidence of isoform\u2010specific changes of \u03b1\u2010adaptins in the brains of LOAD subjects. Antibodies that were verified to recognise AP2A1, but not AP2A2, labelled neurofibrillary tangles of LOAD patients. The findings extend our understanding of AP\u20102 proteins in the human brain in healthy and diseased states.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12776","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T06:31:00Z","timestamp":1637821860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Alpha adaptins show isoform\u2010specific association with neurofibrillary tangles in Alzheimer's disease"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9876-8920","authenticated-orcid":false,"given":"Sukanya","family":"Srinivasan","sequence":"first","affiliation":[{"name":"Sanders\u2010Brown Center on Aging University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozsef","family":"Gal","sequence":"additional","affiliation":[{"name":"Spinal Cord and Brain Injury Research 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