title: Subcellular Changes in Bridging Integrator 1 Protein Expression in the Cerebral Cortex During the Progression of Alzheimer Disease Pathology.
abstract: Genome-wide association studies have established BIN1 (Bridging Integrator 1) as the most significant late-onset Alzheimer disease (AD) susceptibility locus after APOE We analyzed BIN1 protein expression using automated immunohistochemistry on the hippocampal CA1 region in 19 patients with either no, mild, or moderate-to-marked AD pathology, who had been assessed by Clinical Dementia Rating and CERAD scores. We also examined the amygdala, prefrontal, temporal, and occipital regions in a subset of these patients. In non-demented controls without AD pathology, BIN1 protein was expressed in white matter, glia, particularly oligodendrocytes, and in the neuropil in which the BIN1 signal decorated axons. With increasing severity of AD, BIN1 in the CA1 region showed: 1) sustained expression in glial cells, 2) decreased areas of neuropil expression, and 3) increased cytoplasmic neuronal expression that did not correlate with neurofibrillary tangle load. In patients with AD, both the prefrontal cortex and CA1 showed a decrease in BIN1-immunoreactive (BIN1-ir) neuropil areas and increases in numbers of BIN1-ir neurons. The numbers of CA1 BIN1-ir pyramidal neurons correlated with hippocampal CERAD neuritic plaque scores; BIN1 neuropil signal was absent in neuritic plaques. Our data provide novel insight into the relationship between BIN1 protein expression and the progression of AD-associated pathology and its diagnostic hallmarks.
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts (SLA, KT, ID); Broad Institute, Cambridge, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts (JAK) Department of Neurology, Boston University School of Medicine, Boston, Massachusetts (SS).
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Adams
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts (SLA, KT, ID); Broad Institute, Cambridge, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts (JAK) Department of Neurology, Boston University School of Medicine, Boston, Massachusetts (SS).
authors.forename: Kathy
authors.initials: K
authors.lastname: Tilton
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts (SLA, KT, ID); Broad Institute, Cambridge, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts (JAK) Department of Neurology, Boston University School of Medicine, Boston, Massachusetts (SS).
authors.forename: James A
authors.initials: JA
authors.lastname: Kozubek
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts (SLA, KT, ID); Broad Institute, Cambridge, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts (JAK) Department of Neurology, Boston University School of Medicine, Boston, Massachusetts (SS).
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts (SLA, KT, ID); Broad Institute, Cambridge, Massachusetts; Brigham and Women's Hospital, Boston, Massachusetts (JAK) idelalle@bu.edu Department of Neurology, Boston University School of Medicine, Boston, Massachusetts (SS). idelalle@bu.edu.
authors.forename: Ivana
authors.initials: I
authors.lastname: Delalle
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D042541:Intracellular Space / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins
keywords: Alzheimer disease; BIN1; Glia; Hippocampus; Neuropil; Pyramidal neurons; White matter