Affiliations: [a] Department of Psychiatry and Psychotherapy, Saarland University Hospital, Saarland University, Homburg, Germany | [b] Institute for Human Genetics and Medical Genetics, Charité University Medicine, Berlin, Germany | [c] Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg | [d] Institute for Biometrics, Epidemiology and Medical Informatics, Saarland University Hospital, Saarland University, Homburg, Germany
Correspondence:
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Correspondence to: Dr. Daniela Hartl, Department of Psychiatry and Psychotherapy, Saarland University Hospital, 66421 Homburg, Germany. Tel.: +49 6841 1626355; Fax: +49 6841 1624270; [email protected]
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.
