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GBF1 (Golgi brefeldin A resistant guanine nucleotide exchange factor 1) regulates protein trafficking, and genetic variants of\n                      <jats:italic>GBF1<\/jats:italic>\n                      are associated with axonal neuropathy, intelligence, and cognitive function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We sought to identify GBF1 neuropathological and molecular alterations using human\n                      <jats:italic>post mortem<\/jats:italic>\n                      brains, 5XFAD mouse brains, and FAD cells, as well as two family\u2010based datasets (total sample size of 2522) to explore candidate\n                      <jats:italic>GBF1<\/jats:italic>\n                      variants associated with AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      GBF1 revealed neuropathological alterations in association with amyloid plaques. Genetic analysis identified\n                      <jats:italic>GBF1<\/jats:italic>\n                      suggestive variants associated with AD. Downregulation of\n                      <jats:italic>GBF1<\/jats:italic>\n                      retarded amyloid beta (A\u03b2) protein precursor maturation and reduced levels of A\u03b2 proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Collectively,\n                      <jats:italic>GBF1<\/jats:italic>\n                      reveals neuropathological alterations in AD, and may lead to AD by a pathogenic mechanism altering A\u03b2 levels and amyloid deposition in the brain.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71271","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:00:17Z","timestamp":1776337217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intracellular protein GBF1 displays significant associations with amyloid pathology in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Sean J.","family":"Miller","sequence":"first","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"},{"name":"Department of Ophthalmology and Visual Science Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Prokopenko","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Bai","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasenjit","family":"Mondal","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigael","family":"Scott","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Gomm","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Child","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolan","family":"Shen","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ward","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Schulte","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Lei","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit McCance Center for Brain Health MassGeneral Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital and Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Hafler","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science Yale School of Medicine  New Haven Connecticut USA"},{"name":"Department of Pathology Yale School of Medicine  New Haven Connecticut USA"},{"name":"The Broad Institute MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changning","family":"Wang","sequence":"additional","affiliation":[{"name":"Athinoula A. 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