Affiliations: [a] Buck Institute for Research on Aging, Novato, CA, USA | [b] Department of Neurology, University of California, San Francisco, CA, USA | [c] Dominican University of California, San Rafael, CA, USA
Correspondence:
[*]
Correspondence to: Varghese John or Dale E. Bredesen, Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA. Tel.: +1 415 4093 3651; Fax: +1 415 209 2230; E-mail: vjohn@buckinstitute.org.
Note: [1] These two authors share senior authorship.
Abstract: A systematic approach was used to identify AβPP-selective BACE inhibitors (ASBI) and to evaluate their in vivo ability to modulate AβPP processing selectively. We identified a bioflavonoid nutritional supplement as a molecular lead that acts as an ASBI in cell models, and show that increasing brain levels of this bioflavonoid through a pro-drug approach leads to reduction of Aβ42 in an Alzheimer's disease mouse model. ASBIs represent a novel class of candidate therapeutic agents for Alzheimer's disease.
