title: Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation.
abstract: To generate a clinical and pathologic phenotype of patients carrying rare loss-of-function mutations in ABCA7, identified in a Belgian Alzheimer patient cohort and in an autosomal dominant family.
  
  
  
  We performed a retrospective review of available data records, medical records, results of CSF analyses and neuroimaging studies, and neuropathology data.
  
  
  
  The mean onset age of the mutation carriers (n = 22) was 73.4 ± 8.4 years with a wide age range of 36 (54-90) years, which was independent of APOE genotype and cerebrovascular disease. The mean disease duration was 5.7 ± 3.0 years (range 2-12 years). A positive family history was recorded for 10 carriers (45.5%). All patient carriers except one presented with memory complaints. The 4 autopsied brains showed typical immunohistochemical changes of late-onset Alzheimer disease.
  
  
  
  All patients carrying a loss-of-function mutation in ABCA7 exhibited a classical Alzheimer disease phenotype, though with a striking wide onset age range, suggesting the influence of unknown modifying factors.
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Tobi
authors.initials: T
authors.lastname: Van den Bossche
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Elise
authors.initials: E
authors.lastname: Cuyvers
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Sieben
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Arne
authors.initials: A
authors.lastname: De Roeck
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Van Cauwenberghe
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: Vermeulen
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Marleen
authors.initials: M
authors.lastname: Van den Broeck
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Laureys
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Peeters
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Mattheijssens
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: From the Neurodegenerative Brain Diseases Group (T.V.d.B., K.S., E.C., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (T.V.d.B., K.S., E.C., S.E., A.S., A.D.R., C.V.C., S.V., M.V.d.B., A.L., K.P., M.M., J.-J.M., P.P.D.D., P.C., C.V.B.), University of Antwerp; Department of Neurology (T.V.d.B., P.C.), Antwerp University Hospital, Edegem; Department of Neurology and Memory Clinic (T.V.d.B., S.E., P.P.D.D.), Hospital Netwerk Antwerp (ZNA), Middelheim and Hoge Beuken; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurosciences (M.V., R.V.), Faculty of Medicine, KU Leuven; Department of Old Age Psychiatry and Memory Clinic (M.V.) and Department of Neurology (R.V.), University Hospitals Leuven, Belgium; and Department of Neurology and Alzheimer Research Center (P.P.D.D.), University of Groningen and University Medical Center Groningen, the Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
chemical_list: C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters; D053327:Apolipoprotein E4; D015415:Biomarkers