{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T09:26:56Z","timestamp":1794043616938,"version":"4.8.0"},"reference-count":98,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2). PCR analyses on genomic DNA samples confirmed that the size of the MUC6 variable number tandem repeat (VNTR) region was highly polymorphic. In a cohort of autopsied subjects with quantitative digital pathology data (n\u2009=\u2009119), the size of the polymorphic region was associated with the severity of pTau pathology in neocortex. In a separate replication cohort of autopsied subjects (n\u2009=\u2009173), more pTau pathology was again observed in subjects with longer VNTR regions (p\u2009=\u20090.031). Unlike MUC6, AP2A2 is highly expressed in human brain. AP2A2 expression was lower in a subset analysis of brain samples from persons with longer versus shorter VNTR regions (p\u2009=\u20090.014 normalizing with AP2B1 expression). Double-label immunofluorescence studies showed that AP2A2 protein often colocalized with neurofibrillary tangles in LOAD but was not colocalized with pTau proteinopathy in progressive supranuclear palsy, or with TDP-43 proteinopathy. In summary, polymorphism in a repeat-rich region near AP2A2 was associated with neocortical pTau proteinopathy (because of the unique repeats, prior genome-wide association studies were probably unable to detect this association), and AP2A2 was often colocalized with neurofibrillary tangles in LOAD.<\/jats:p>","DOI":"10.1093\/jnen\/nlz116","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T05:10:30Z","timestamp":1574313030000},"page":"3-21","source":"Crossref","is-referenced-by-count":34,"title":["Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the <i>MUC6<\/i> Gene, Near the <i>AP2A2<\/i> Gene"],"prefix":"10.1093","volume":"79","author":[{"given":"Yuriko","family":"Katsumata","sequence":"first","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Fardo","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D","family":"Bachstetter","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey C","family":"Artiushin","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang-Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Wei","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena J","family":"Brzezinski","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela 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Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indumati","family":"Patel","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging (YK, DWF, ADB, SCA, W-XW, AW, LJB, BGN, QH, ELA, SA, IP, DAP, DMN, DWW, GAJ, LJVE, PTN); Department of Biostatistics (YK, DWF); Spinal Cord & Brain Injury Research Center (ADB); Department of Neuroscience (ADB, DWW, LJVE); Department of Epidemiology (ELA); Department of Neurology (DWW, GAJ); Department of Physiology (BCS, SE); and Department of Pathology (W-XW, JHN, PTN), University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin 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