title: Amyloid-β Protein Precursor Cleavage Products in Postmortem Ventricular Cerebrospinal Fluid of Alzheimer's Disease Patients.
abstract: Accumulation and aggregation of amyloid-β (Aβ) are considered etiologic processes in Alzheimer's disease (AD). However, the roles of other AβPP cleavage products in disease pathology remain elusive. Here, we measured levels of the major secreted AβPP processing products sAβPPα, sAβPPβ, and Aβ species in postmortem collected ventricular CSF of 196 AD patients and 74 controls. In AD we identified Aβ₄₂ to decrease continuously with progressing Braak stages, whereas Aβ₄₀ was upregulated in early stages of the disease (Braak stage 4) and down-regulated with progressing pathology. Interestingly, both sAβPPα and sAβPPβ were upregulated in AD as compared to controls (sAβPPα, p = 0.02; sAβPPβ, p = 0.01). Moreover, we observed a strong positive correlation of both alternative AβPP processing products, sAβPPα and sAβPPβ (r²= 0.781; p <  0.0001). Together, our results argue for generally enhanced AβPP processing in AD patients and emphasize the necessity of analyzing the roles of all AβPP processing products in AD pathology.
authors.affiliation: Department of Psychiatry and Psychotherapy, Saarland University Hospital, Saarland University, Homburg, Germany.|Institute for Human Genetics and Medical Genetics, Charité University Medicine, Berlin, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hartl
authors.affiliation: Department of Psychiatry and Psychotherapy, Saarland University Hospital, Saarland University, Homburg, Germany.|Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Psychiatry and Psychotherapy, Saarland University Hospital, Saarland University, Homburg, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayhaus
authors.affiliation: Department of Psychiatry and Psychotherapy, Saarland University Hospital, Saarland University, Homburg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pichler
authors.affiliation: Institute for Biometrics, Epidemiology and Medical Informatics, Saarland University Hospital, Saarland University, Homburg, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Schöpe
authors.affiliation: Institute for Biometrics, Epidemiology and Medical Informatics, Saarland University Hospital, Saarland University, Homburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.affiliation: Department of Psychiatry and Psychotherapy, Saarland University Hospital, Saarland University, Homburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Riemenschneider
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; amyloid-β protein precursor; soluble AβPP; ventricular cerebrospinal fluid