PMID- 37260026
OWN - NLM
STAT- MEDLINE
DCOM- 20231229
LR  - 20240106
IS  - 1552-5279 (Electronic)
IS  - 1552-5260 (Linking)
VI  - 19
IP  - 12
DP  - 2023 Dec
TI  - Fc N-glycosylation of autoreactive Abeta antibodies as a blood-based biomarker for 
      Alzheimer's disease.
PG  - 5563-5572
LID - 10.1002/alz.13124 [doi]
AB  - INTRODUCTION: Naturally occurring autoantibodies (nAbs) against the pathologic 
      isoform of amyloid beta (Abeta(42) ) were found in body fluids and indicate a 
      systemic B cell response that may prevent Alzheimer's disease (AD) onset. 
      N-glycans attached to immunoglobulin G-Fab/Fc fragments are features that 
      influence their mechanism of action. The aim was to study the role of N-glycans 
      in nAbs-Abeta(42) . METHODS: nAbs-Abeta(42) were isolated from AD patients and 
      age-/sex-matched controls (n = 40) and immunoglobulin preparations. 
      Glycosylated/deglycosylated nAbs-Abeta(42) were analyzed for their effect on Abeta(42) 
      's aggregation, toxicity, and phagocytosis. Glycan structure was analyzed using 
      matrix assisted laser desorption ionization time of flight mass spectrometry. 
      RESULTS: Deglycosylation of nAbs-Abeta42 had a major impact on Abeta(42) 's 
      aggregation/toxicity/phagocytosis. The glycan structure showed considerable 
      differences between AD and controls. We were able to predict disease status with 
      a sensitivity/specificity of 95% (confidence interval [CI]: 76.4-99.7%)/100% (CI: 
      83.9-100%). DISCUSSION: N-glycosylation has been identified as a critical 
      attribute maintaining the beneficial effects of autoreactive Abeta antibodies. These 
      data have consequences for the development of monocloncal Abeta antibodies and may 
      open new avenues for diagnostics.
CI  - (c) 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on 
      behalf of Alzheimer's Association.
FAU - Kronimus, Yannick
AU  - Kronimus Y
AD  - Chair of Geriatric Medicine and Center for Translational Neuro- and Behavioral 
      Sciences, University Duisburg-Essen, Essen, Germany.
FAU - Albus, Alexandra
AU  - Albus A
AD  - Chair of Geriatric Medicine and Center for Translational Neuro- and Behavioral 
      Sciences, University Duisburg-Essen, Essen, Germany.
FAU - Hasenberg, Mike
AU  - Hasenberg M
AD  - Imaging Center Essen (Electron Microscopy), University Hospital Essen, University 
      Duisburg-Essen, Essen, Germany.
FAU - Walkenfort, Bernd
AU  - Walkenfort B
AD  - Imaging Center Essen (Electron Microscopy), University Hospital Essen, University 
      Duisburg-Essen, Essen, Germany.
FAU - Seifert, Marc
AU  - Seifert M
AD  - Institute of Cell Biology (Cancer Research), Medical Faculty, University 
      Duisburg-Essen, Essen, Germany.
FAU - Budeus, Bettina
AU  - Budeus B
AD  - Institute of Cell Biology (Cancer Research), Medical Faculty, University 
      Duisburg-Essen, Essen, Germany.
FAU - Gronewold, Janine
AU  - Gronewold J
AD  - Department of Neurology, University Hospital Essen, University Duisburg-Essen, 
      Essen, Germany.
FAU - Hermann, Dirk M
AU  - Hermann DM
AD  - Department of Neurology, University Hospital Essen, University Duisburg-Essen, 
      Essen, Germany.
FAU - Ross, J Alexander
AU  - Ross JA
AD  - Chair of Geriatric Medicine and Center for Translational Neuro- and Behavioral 
      Sciences, University Duisburg-Essen, Essen, Germany.
FAU - Lochnit, Gunter
AU  - Lochnit G
AD  - Protein Analytics, Department of Biochemistry, Justus Liebig University Giessen, 
      Giessen, Germany.
FAU - Galuska, Sebastian P
AU  - Galuska SP
AD  - Institute of Reproductive Biology, Research Institute for Farm Animal Biology 
      (FBN), Dummerstorf, Germany.
FAU - Marcus, Katrin
AU  - Marcus K
AD  - Medizinisches Proteom-Center, Medical Faculty; Medical Proteome Analysis, Center 
      for Proteindiagnostics (PRODI), Ruhr-University Bochum, Bochum, Germany.
FAU - Sitek, Barbara
AU  - Sitek B
AD  - Medizinisches Proteom-Center, Medical Faculty; Medical Proteome Analysis, Center 
      for Proteindiagnostics (PRODI), Ruhr-University Bochum, Bochum, Germany.
AD  - Klinik fur Anasthesiologie, Intensivmedizin und Schmerztherapie, 
      Universitatsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany.
FAU - Klotsche, Jens
AU  - Klotsche J
AD  - Epidemiology Unit, German Rheumatism Research Center Berlin - a Leibniz Institute 
      (DRFZ), Berlin, Germany.
FAU - Mengel, David
AU  - Mengel D
AD  - Chair of Geriatric Medicine and Center for Translational Neuro- and Behavioral 
      Sciences, University Duisburg-Essen, Essen, Germany.
AD  - Laboratory for Neurodegenerative Research, Ann Romney Center for Neurologic 
      Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, 
      Massachusetts, USA.
FAU - Neumann, Sascha
AU  - Neumann S
AD  - Chair of Geriatric Medicine and Center for Translational Neuro- and Behavioral 
      Sciences, University Duisburg-Essen, Essen, Germany.
FAU - Dodel, Richard
AU  - Dodel R
AD  - Chair of Geriatric Medicine and Center for Translational Neuro- and Behavioral 
      Sciences, University Duisburg-Essen, Essen, Germany.
LA  - eng
GR  - 233-1.08.03.03-031-68079/Protein research Unit Ruhr within Europe/
GR  - Ernst und Margot Faber-Stiftung/
GR  - SE1885/2-2/Deutsche Forschungsgemeinschaft/
GR  - SE1885/4-1/Deutsche Forschungsgemeinschaft/
GR  - 70112628/Deutsche Krebshilfe/
PT  - Journal Article
DEP - 20230601
PL  - United States
TA  - Alzheimers Dement
JT  - Alzheimer's & dementia : the journal of the Alzheimer's Association
JID - 101231978
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Autoantibodies)
RN  - 0 (Biomarkers)
RN  - 0 (Polysaccharides)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Humans
MH  - *Alzheimer Disease/pathology
MH  - Amyloid beta-Peptides
MH  - Glycosylation
MH  - Autoantibodies
MH  - Biomarkers
MH  - Polysaccharides
MH  - Peptide Fragments
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - N-glycosylation
OT  - amyloid beta
OT  - autoantibodies
OT  - biomarker
OT  - immunoglobulin G
OT  - nAbs-Abeta42
OT  - naturally occurring autoantibodies
EDAT- 2023/06/01 13:09
MHDA- 2023/12/29 06:43
CRDT- 2023/06/01 07:03
PHST- 2023/01/22 00:00 [revised]
PHST- 2022/10/19 00:00 [received]
PHST- 2023/01/24 00:00 [accepted]
PHST- 2023/12/29 06:43 [medline]
PHST- 2023/06/01 13:09 [pubmed]
PHST- 2023/06/01 07:03 [entrez]
AID - 10.1002/alz.13124 [doi]
PST - ppublish
SO  - Alzheimers Dement. 2023 Dec;19(12):5563-5572. doi: 10.1002/alz.13124. Epub 2023 
      Jun 1.