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Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP‐CTFs), associated with tau pathology stages, in Alzheimer's disease
Author(s) -
Sergeant Nicolas,
David JeanPhilippe,
Champain Danie,
Ghestem Antoine,
Wattez Annick,
Delacourte André
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00901.x
Subject(s) - amyloid precursor protein , β amyloid , amyloid (mycology) , disease , alzheimer's disease , neurodegeneration , senile plaques , pathology , amyloid β , medicine , chemistry
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 β‐amyloid peptide (Aβ) 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 Aβ products and its relationship with tau pathology, which could reflect the basic aetiological mechanisms of AD.