title: Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis.
abstract: Increased APP (amyloid precursor protein) processing causes β-amyloid (Aβ) accumulation in autosomal dominant Alzheimer's disease (AD), but it is unclear if it also affects sporadic Aβ accumulation. We tested healthy controls and patients with mild cognitive symptoms (N=331) in the BioFINDER study, using cerebrospinal fluid (CSF) Aβ40 as a surrogate for amyloidogenic APP processing. We find that levels of brain Aβ fibrils (measured by 18F-flutemetamol PET) are independently associated with high CSF Aβ40 (P<0.001) and APOE ɛ4 (P<0.001). The association between CSF Aβ40 and brain Aβ is stronger in APOE ɛ4-negative than in positive people (P=0.0080). The results are similar for CSF Aβ38 and for a combination of CSF Aβ38 and CSF Aβ40. In conclusion, sporadic Aβ accumulation may be partly associated with increased amyloidogenic APP production, especially in APOE ɛ4-negative subjects. The risk for sporadic AD may consequently depend on increased Aβ production, in addition to decreased Aβ clearance.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Simrisbanvägen 14, Malmö 212 24, Sweden.|Memory Clinic, Skåne University Hospital, Simrisbanvägen 14, Malmö 212 24, Sweden.|Department of Neurology, Skåne University Hospital, Getingevägen 4, Lund 222 41, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Simrisbanvägen 14, Malmö 212 24, Sweden.|Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging, San Francisco Veterans Affairs Medical Center (SFVAMC) campus, 4150 Clement Street, University of California, San Francisco, California 94121, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Insel
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Simrisbanvägen 14, Malmö 212 24, Sweden.|Department of Neurology, Skåne University Hospital, Getingevägen 4, Lund 222 41, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Palmqvist
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Simrisbanvägen 14, Malmö 212 24, Sweden.|Memory Clinic, Skåne University Hospital, Simrisbanvägen 14, Malmö 212 24, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Stomrud
authors.affiliation: Department of Clinical Sciences, Diagnostic Radiology, Lund University, Box 117, Lund 221 00, Sweden.|Center for Medical Imaging and Physiology, Skåne University Hospital, Getingevägen 4, Lund 222 41, Sweden.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Westen
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Simrisbanvägen 14, Malmö 212 24, Sweden.|Memory Clinic, Skåne University Hospital, Simrisbanvägen 14, Malmö 212 24, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.|Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal 431 80, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal 431 80, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Simrisbanvägen 14, Malmö 212 24, Sweden.|Memory Clinic, Skåne University Hospital, Simrisbanvägen 14, Malmö 212 24, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000172:deficiency* / Q000235:genetics; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4