title: BRI2-BRICHOS is increased in human amyloid plaques in early stages of Alzheimer's disease.
abstract: BRI2 protein binds amyloid precursor protein to halt amyloid-β production and inhibits amyloid-β aggregation via its BRICHOS-domain suggesting a link between BRI2 and Alzheimer's disease (AD). Here, we investigate the possible involvement of BRI2 in human AD pathogenesis. BRI2 containing BRICHOS-domain was increased up to 3-fold in AD hippocampus (p = 0.003, n = 14/group). Immunohistochemistry showed BRI2 deposits associated with amyloid-β plaques in early pathologic stages (Braak-III; Thal-2/3). We observed a decrease in the protein levels of ADAM10 (p = 0.02) and furin (p = 0.066), as well as an increase in SPPL2b (p < 0.0001) in AD hippocampus. Because these enzymes are involved in BRI2 processing, their changes may lead to aberrant processing of BRI2 promoting its deposition and likely affecting BRI2 function. Loss of BRI2 function in AD was supported by the decreased presence of BRI2-amyloid precursor protein complexes in the hippocampus of AD patients compared with control subjects. In conclusion, our data obtained from human samples indicate that in early stages of AD there is an increased deposition of BRI2, which likely leads to impaired BRI2 function thereby influencing AD pathophysiology.
authors: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands; Neurochemistry Laboratory, VU University Medical Center, Amsterdam, the Netherlands; Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: m.delcampomilan@vumc.nl.
authors: Marta
authors: M
authors: Del Campo
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Jeroen J M
authors: JJ
authors: Hoozemans
authors: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands; Neurochemistry Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
authors: Lois-Lee
authors: LL
authors: Dekkers
authors: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors: Annemieke J
authors: AJ
authors: Rozemuller
authors: Department of Neuropathology, Heinrich Heine University Medical School, Düsseldorf, Germany.
authors: Carsten
authors: C
authors: Korth
authors: Department of Neuropathology, Heinrich Heine University Medical School, Düsseldorf, Germany.
authors: Andreas
authors: A
authors: Müller-Schiffmann
authors: Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
authors: Philip
authors: P
authors: Scheltens
authors: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands; Neurochemistry Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
authors: Marinus A
authors: MA
authors: Blankenstein
authors: Department of Medical Oncology and OncoProteomics Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
authors: Connie R
authors: CR
authors: Jimenez
authors: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands; Neurochemistry Laboratory, VU University Medical Center, Amsterdam, the Netherlands; Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands; Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands.
authors: Robert
authors: R
authors: Veerhuis
authors: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, the Netherlands; Neurochemistry Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
authors: Charlotte E
authors: CE
authors: Teunissen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D046912:Multiprotein Complexes / Q000378:metabolism; D058225:Plaque, Amyloid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C120083:ITM2B protein, human; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes
keywords: Alzheimer's disease; Amyloid plaques; BRI2; Human hippocampus; Pathogenesis