Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer's
disease beta-amyloid production.
Rezai-Zadeh K, Shytle RD, Bai Y, Tian J, Hou H, Mori T, Zeng J, Obregon
D, Town T, Tan J.

Rashid Laboratory for Developmental Neurobiology, Silver Child
Development Center, Department of Psychiatry & Behavioral Medicine,
College of Medicine, University of South Florida, Tampa, FL 33613, USA.

Glycogen synthase kinase 3 (GSK-3) dysregulation is implicated in the
two Alzheimer's disease (AD) pathological hallmarks: beta-amyloid
plaques and neurofibrillary tangles. GSK-3 inhibitors may abrogate AD
pathology by inhibiting amyloidogenic gamma-secretase cleavage of
amyloid precursor protein (APP). Here, we report that the citrus
bioflavonoid luteolin reduces amyloid-beta peptide (Abeta) generation in
both human "Swedish" mutant APP transgene-bearing neuron-like cells and
primary neurons. We also find that luteolin induces changes consistent
with GSK-3 inhibition that 1) decrease amyloidogenic gamma-secretase APP
processing, and 2) promote presenilin-1 (PS1) carboxyl-terminal fragment
(CTF) phosphorylation. Importantly, we find GSK-3alpha activity is
essential for both PS1 CTF phosphorylation and PS1-APP interaction. As
validation of these findings in vivo, we find that luteolin, when
applied to the Tg2576 mouse model of AD, decreases soluble Abeta levels,
reduces GSK-3 activity, and disrupts PS1-APP association. In addition,
we find that Tg2576 mice treated with diosmin, a glycoside of a
flavonoid structurally similar to luteolin, display significantly
reduced Abeta pathology. We suggest that GSK-3 inhibition is a viable
therapeutic approach for AD by impacting PS1 phosphorylation-dependent
regulation of amyloidogenesis.

PMID: 18410522

The full paper can be found at --
http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1582-4934.2008.00344.x

From the paper luteolin has poor oral bioavailability but diosmin is
well absorbed and has a plasma half-life > 26 hours.

Diosmin is readily available as a supplement.
http://www.iherb.com/Search.aspx?c=1&st=l&kw=diosmin