Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease.
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.
Sergeant
Nicolas
N
INSERM U422, 1 Place de Verdun, 59045 Lille Cedex, France.
David
Jean-Philippe
JP
Champain
Danie
D
Ghestem
Antoine
A
Wattez
Annick
A
Delacourte
André
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011446:Prospective Studies; D011499:Protein Processing, Post-Translational; D012995:Solubility; D016875:tau Proteins / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D016875:tau Proteins