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Alterations in the Balance of Amyloid-β Protein Precursor Species in the Cerebrospinal Fluid of Alzheimer's Disease Patients

Lopez-Font, I; Boix, CP; Zetterberg, H; Blennow, K; Sáez-Valero, J; (2017) Alterations in the Balance of Amyloid-β Protein Precursor Species in the Cerebrospinal Fluid of Alzheimer's Disease Patients. Journal of Alzheimer's Disease 10.3233/JAD-161275. (In press). Green open access

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Abstract

We recently demonstrated that soluble forms of the amyloid-β protein precursor (sAβPP) assemble into multimeric complexes in cerebrospinal fluid (CSF), which contributes to the underestimation of specific sAβPP species when assessed by ELISA. To circumvent this issue, we analyzed by SDS-PAGE large fragments of sAβPP and their variants in the CSF from Alzheimer's disease (AD; n = 20) and control (n = 20) subjects, probing with specific antibodies against particular domains. Similar levels of sAβPPα and sAβPPβ protein were found in CSF samples from AD and controls, yet there appeared to be a shift in the balance of the soluble full-length AβPP (sAβPPf) species in AD samples, with a decrease in the proportion of the lower (∼100 kDa) band relative to the upper (∼120 kDa) band. Similar differences were observed in the contribution of the major KPI-immunoreactive AβPP species. CSF samples also displayed differences in the correlations of AβPP species with classical AD biomarkers, particularly with respect to the Aβ42 peptide. The differences reveal alterations that probably reflect pathophysiological changes in the brain.

Type: Article
Title: Alterations in the Balance of Amyloid-β Protein Precursor Species in the Cerebrospinal Fluid of Alzheimer's Disease Patients
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.3233/JAD-161275
Publisher version: http://dx.doi.org/10.3233/JAD-161275
Language: English
Additional information: The final publication is available at IOS Press through http://dx.doi.org/10.3233/JAD-161275.
Keywords: Alzheimer’s disease, AβPP, KPI, biomarker, cerebrospinal fluid, sAβPPf, sAβPPα, sAβPPβ
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience
URI: http://discovery.ucl.ac.uk/id/eprint/1549756
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