Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease
Article first published online: 7 MAY 2002
Journal of Neurochemistry
Volume 81, Issue 4, pages 663–672, May 2002
How to Cite
Sergeant, N., David, J.-P., Champain, D., Ghestem, A., Wattez, A. and Delacourte, A. (2002), Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP-CTFs), associated with tau pathology stages, in Alzheimer's disease. Journal of Neurochemistry, 81: 663–672. doi: 10.1046/j.1471-4159.2002.00901.x
- Issue published online: 7 MAY 2002
- Article first published online: 7 MAY 2002
- Received November 27, 2001; revised manuscript received December 13, 2001; accepted January 3, 2002.
- Alzheimer's disease;
- amyloid precursor protein;
- pathological tau proteins;
- proteolytic processing
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.