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Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease.

Nicolas Sergeant·Jean-Philippe David·Danie Champain·Antoine Ghestem·Annick Wattez·André Delacourte
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Abstract

Amyloid precursor protein (APP) dysfunction is a key aetiologic agent in Alzheimer's disease (AD). The processing of this transmembrane protein generates carboxy terminal fragments (CTFs) upstream of beta-amyloid peptide (Abeta) production. The physiologic significance of APP-CTFs is still poorly understood, as well as the relationship that could link APP dysfunction and tau pathology in familial and non-familial AD (non-FAD). In the present study, we have investigated the quantitative and qualitative changes of APP-CTFs in different brain areas of non-demented and demented patients from a prospective and multidisciplinary study. A significant decrease of the five APP-CTFs was observed, which correlated well with the progression of tau pathology, in most cases with infraclinical AD and AD, either familial or non-FAD. Furthermore, solubility properties and the ratio between the five bands were also modified, both in the Triton-soluble and/or -insoluble fractions. Together, we show here for the first time a modification directly observed on APP-CTFs upstream of Abeta products and its relationship with tau pathology, which could reflect the basic aetiological mechanisms of AD.

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AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-Protein PrecursorBlotting, WesternBrainBrain ChemistryDisease ProgressionElectrophoresis, Gel, Two-DimensionalHumansMiddle AgedPeptide FragmentsPhosphorylationPrecipitin TestsProspective StudiesProtein Processing, Post-TranslationalSolubilitytau ProteinsJournal ArticleResearch Support, Non-U.S. Gov't

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Nicolas Sergeant, Jean-Philippe David, Danie Champain, Antoine Ghestem, Annick Wattez, André Delacourte. 2002. Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease.. https://doi.org/10.1046/j.1471-4159.2002.00901.x

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