Preprint
Article
Results of BACE1-Inhibitor Clinical Trials Confirm Key Predictions For App-Independent Generation of Beta-Amyloid in Sporadic AD
This version is not peer-reviewed.
Submitted:
05 April 2018
Posted:
06 April 2018
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Abstract
The present article analyzes the results of recent clinical trials of beta secretase inhibition in sporadic Alzheimer’ disease (SAD), considers the striking dichotomy between successes in tests of BACE1 inhibitors in healthy subjects and familial AD (FAD) models versus persistent failures of clinical trials and interprets it as a confirmation of key predictions for a mechanism of APP-independent, beta secretase inhibition-resistant production of beta amyloid in SAD, previously proposed by us. In the light of this concept, FAD and SAD should be regarded as distinctly different diseases as far as beta-amyloid generation mechanisms are concerned, and whereas beta secretase inhibition would be neither applicable nor effective in treatment of SAD, the BACE1 inhibitor(s) deemed failed in SAD trials could be perfectly suitable for treatment of FAD. Moreover, targeting the aspects of AD other than cleavages of the APP by beta and alpha secretases should have analogous impacts in both FAD and SAD.
Keywords:
Alzheimer’s disease (AD)
; amyloid precursor protein (APP)
; familial AD (FAD)
; sporadic AD (SAD)
; BACE1 inhibitors
; APP-independent generation of beta amyloid
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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