Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease

Volloch, Vladimir; Rits, Sophia

doi:10.3390/medsci6020045

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Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease

Vladimir Volloch

^1,* and

Sophia Rits

^2,3

Deptartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA

Howard Hughes Medical Institute at Children’s Hospital, Boston, MA 02115, USA

Deptartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA

Author to whom correspondence should be addressed.

Med. Sci. 2018, 6(2), 45; https://doi.org/10.3390/medsci6020045

Received: 26 April 2018 / Revised: 20 May 2018 / Accepted: 29 May 2018 / Published: 2 June 2018

(This article belongs to the Collection Advances in the Pathogenesis of Neurodegenerative Diseases)

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Abstract

The present review analyzes the results of recent clinical trials of β secretase inhibition in sporadic Alzheimer’s disease (SAD), considers the striking dichotomy between successes in tests of β-site Amyloid Precursor Protein-Cleaving Enzyme (BACE) inhibitors in healthy subjects and familial Alzheimer’s disease (FAD) models versus persistent failures of clinical trials and interprets it as a confirmation of key predictions for a mechanism of amyloid precursor protein (APP)-independent, β secretase inhibition-resistant production of β amyloid in SAD, previously proposed by us. In light of this concept, FAD and SAD should be regarded as distinctly different diseases as far as β-amyloid generation mechanisms are concerned, and whereas β secretase inhibition would be neither applicable nor effective in the treatment of SAD, the β-site APP-Cleaving Enzyme (BACE) inhibitor(s) deemed failed in SAD trials could be perfectly suitable for the treatment of FAD. Moreover, targeting the aspects of Alzheimer’s disease (AD) other than cleavages of the APP by β and α secretases should have analogous impacts in both FAD and SAD. View Full-Text

Keywords: Alzheimer’s disease; amyloid precursor protein; familial Alzheimer’s disease; sporadic Alzheimer’s disease; β-site amyloid precursor protein-cleaving enzyme 1 inhibitors; amyloid precursor protein-independent generation of β amyloid

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MDPI and ACS Style

Volloch, V.; Rits, S. Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease. Med. Sci. 2018, 6, 45. https://doi.org/10.3390/medsci6020045

AMA Style

Volloch V, Rits S. Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease. Medical Sciences. 2018; 6(2):45. https://doi.org/10.3390/medsci6020045

Chicago/Turabian Style

Volloch, Vladimir, and Sophia Rits. 2018. "Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease" Medical Sciences 6, no. 2: 45. https://doi.org/10.3390/medsci6020045

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Results of Beta Secretase-Inhibitor Clinical Trials Support Amyloid Precursor Protein-Independent Generation of Beta Amyloid in Sporadic Alzheimer’s Disease

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