1. Alzheimer's disease is a major health concern that causes cognitive decline through β-amyloid accumulation and plaque formation in the brain. 2. Resveratrol has been shown to inhibit β-amyloid accumulation by binding to the proteins and changing their conformation to a non-toxic form, reducing plaque formation and neuronal damage. 3. While studies support resveratrol's potential as a therapeutic for Alzheimer's disease, long-term clinical trials in humans are still needed to confirm its safety and efficacy.

1. Alzheimer’s disease (AD) is a disease of concern due to its many implications on the individual,
family and friends, and even the economy.1,2 The pathogenesis of AD is not widely understood,
but one of the main proposed causes of cognitive impairment in AD is β-amyloid accumulation
and toxicity in the brain. This accumulation of β-amyloid proteins in the cortex and hippocampus
of individuals with AD causes neurological degeneration.3 Through our research, we aim to
explain resveratrol (Res) action in inhibiting β-amyloid accumulation and toxicity and to propose
Res as a potential therapeutic agent in the prevention and treatment of AD. Future long-term
research is needed in this area to ensure that Res is a safe and effective treatment on human
subjects at risk of developing or suffering from AD.
Resveratrol May Reduce β-Amyloid Plaques Aiding in the Treatment and Prevention of
Alzheimer's Disease
Erin Meyer, Kendra Parker, Mia Matthews
Department of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO, USA
AD affects 1 in 10 Americans over 65 years old1 and is accompanied with a loss of memory and
language, the inability to learn and perform calculations, and a distorted perception of space.
Patients may also experience depression, delusions and other cognitive impairments. AD poses
a great emotional and economical burden on those whose lives it effects directly as well as
society as a whole. There is currently no cure for the condition and very few FDA approved,
efficacious treatments exist.2 One major feature of AD is the abnormal aggregation of β-amyloid
proteins resulting in the accumulation of neuritic plaques causing neuronal damage and loss.4, 2,
5, 3 Ineffective drugs accompanied with intolerable side effects have perpetuated the demand for
alternative treatments.3 Research has suggested that Res, a polyphenol found in grapes,
berries, tea and soy,6,7 may reduce this accumulation and consequent neuronal deterioration.
Therefore, Res may be beneficial in AD treatment and prevention.2
Introduction
myteastories.com
Physiology
AD is a serious condition accompanied with significant emotional and economic burdens and its
prevalence is on the rise. Research aimed towards the treatment and prevention of AD is
extremely crucial for our growing older adult population and ineffective drugs with intolerable side
effects stimulate the demand for alternative treatments.3 Research has shown that Res could be a
potential therapeutic tool used to combat this disease due to it’s action against β-amyloid
accumulation and toxicity via binding to β-amyloid proteins and changing its conformation. This
results in the inhibition of their accumulation and formation of neuritic plaques as well as reducing
its toxicity. Therefore, Res is an important compound of interest for future research on interventions
against the development of AD. Although many studies have been conducted in vitro and in animal
models, Res’s effectiveness and long term safety in humans remains unknown and therefore
warrants the need for large scale, long-term clinical trials using resveratrol and its derivatives/
synthetics.
Res has been theorized to work through several mechanisms including actions as an anti-
inflammatory and antioxidant, modulating cell death and cell pathways, preventing telomere
shortening and protecting the blood brain barrier.7, 8, 5, 9 Much of the current research targets Res’s
ability to inhibit β-amyloid protein aggregation.8, 9, 10 In the development of AD, an increase in
reactive oxygen species (ROS) contributes to an increase in β-amyloid protein production and
related oxidative stress. Additionally, the amyloid precursor protein, a transmembrane glycoprotein,
is normally cleaved by β, γ and α-secretase, but in AD, it is abnormally cleaved and the α-secretase
does not function. These occurrences result in the formation of neuritic plaques causing neuronal
damage to mitochondrial and cellular membranes in the brain.3 Research has shown that Res may
bind to β -amyloid proteins which interferes with their accumulation and changes the conformation
to a nontoxic form, thereby decreasing toxicity and reducing neuronal damage.8 Related studies
have demonstrated Res’s ability to stimulate protein kinase C isoforms which may inactivate
GSK3B, a protein coding gene which is commonly overexpressed in AD. This further contributes to
Res’s protection against Aβ toxicity.7
Similar Compounds
Objectives
1. To explain the implications and pathogenesis of Alzheimer’s disease
2. To explain Resveratrol’s and similar compounds’ role in the treatment and prevention of AD
1. Pasinetti GM, Wang J, Ho L, Zhao W, Dubner L. Roles of Resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochemica et Biophysica Acta. 2014; 1852: 1202-1208. doi: http://dx.doi.org/10.1016/j.bbadis.2014.10.006
2. Pasinetti GD. Novel Role of Red Wine-Derived Polyphenols in the Prevention of Alzheimer’s Disease Dementia and Brain Pathology: Experimental Approaches and Clinical Implications. Planta Med. 2012; 78: 1614-1619. doi: http://dx.doi.org/ 10.1055/s-0032-1315377
3. Ma T, Tan MS, Yu JT, Tan L. Resveratrol as a Therapeutic Agent for Alzheimer’s Disease. BioMed Research International. 2014; 2014: 1-14. doi: http://dx.doi.org/10.1155/2014/350516
4. Brain Tour. Alzheimer’s Association Web site. https://www.alz.org/braintour/plaques.asp. Published 2011. Accessed March 10, 2016.
5. Malhotra A, Bath S, Elbarby F. An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol. Oxidative Medicine and Cellular Longevity. 2014; 2015: 1-15. doi: http://dx.doi.org/10.1155/2015/803971
6. Rege SD, Geetha T, Griffin GD, Broderick TL, Babu JR. Neuroprotective effects of resveratrol in Alzheimer disease pathology. Frontiers in Aging Neuroscience. 2014; 6: 1-12. doi: 10.3389/fnagi.2014.00218
7. Yao Y, Li J, Niu Y et al. Resveratrol inhibits oligomeric Aβ-induced microglial activation via NADPH oxidase. Molecular Medicine Reports. 2015; 12: 6133-6139. doi: 10.3892/mmr.2015.4199
8. Bastianetto S, Menard C, Quirion R. Neuroprotective action of resveratrol. Biochemica et Biophysica Acta. 2014; 1852: 1195-1201. doi: http://dx.doi.org/10.1016/j.bbadis.2014.09.011
9. Zhao HF, Li N, Wang Q, Cheng XJ, Li XM, Liu TT. Resveratrol decreases the insoluble Aβ 1- 42 level in hippocampus and protects the integrity of the blood-brain barrier in AD rats. Neuroscience. 2015; 310: 641-649. doi: http://dx.doi.org/10.1016/j.neuroscience.2015.10.006
10. Albani D, Polito L, Signorini A, Forloni G. Neuroprotective properties of resveratrol in different neurodegenerative disorders. BioFactors. 2010; 5: 370-376. doi: 10.1002/biof.118
11. Coradini K, Lima FO, Oliveira CM et al. Co-encapsulation of resveratrol and curcumin in lipid-core nanocapsules improves their in vitro antioxidant effects. European Journal of Pharmaceutics and Biopharmaceutics. 2014; 88: 178-185. doi: http://dx.doi.org/10.1016/j.ejpb.2014.04.009
12. Fabris S, Momo F, Ravagnan G, Stevanato R. Antioxidant properties of resveratrol and piceid on lipid peroxidation in micelles and monolamellar liposomes. Biophysical Chemistry. 2008; 135: 76-83. doi: doi:10.1016/j.bpc.2008.03.005
13.Tellone E, Galtieri A, Russo A, Giardina B, Ficarra S. Resveratrol: A Focus on Several Neurodegenerative Disease. Oxidative Medicine and Cellular Longevity. 2014; 2015: 1-14. doi: http://dx.doi.org/10.1155/2015/392169
14. Zhao W, Wang J, Bi W et al. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction. Neurochemistry International. 2015; 89: 191-197. doi: http://dx.doi.org/10.1016/j.neuint.2015.07.023
15. Kim
HJ, Lee KW, Lee HJ. Protective Effects of Piceatannol against Beta-Amyloid–Induced Neuronal Cell Death. Annals New York Academy of Sciences. 2007; 1095: 473-482. doi: 10.1196/annals.1397.051
16. Patterson C, Feightner JW, Garcia A, Hsiung GYR, MacKnight C, Sadovnick AD. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ. 2008; 178: 548-556.
17. Lifelong brain-stimulating habits linked to lower Alzheimer’s protein levels. UC Berkeley Web site. http://news.berkeley.edu/2012/01/23/engaged-brain-amyloid-alzheimers/ Published January 23, 2012. Accessed April 12, 2016.
References
Compound/
Delivery
System
Defini5on Benefits
Lipid
core
nanocapsules
with
resveratrol
Made
up
of
an
oil
core
formed
by
a
dispersion
of
a
liquid
lipid
and
a
solid
lipid
surrounded
by
a
polymeric
wall
and
a
par5cle-­‐water
interface,
which
is
stabilized
by
polysorbate
80.11
This
delivery
system
may
stabilize
photolabile
substances,
control
drug
release,
improve
effec5veness,
and
increase
cerebral
distribu5on
of
the
compound.
They
may
increase
the
photostability
of
resveratrol,
beCer
target
the
compound
to
the
brain
5ssue,
improve
the
compound’s
an5glioma
ac5vity
and
mi5gate
AD
(based
on
the
Aβ
1-­‐42
model).11
Piceid The
glycoside
form
of
resveratrol.12 Piceid
exhibits
high
scavenging
ac5vity
against
radicals
and
thus
may
aid
in
the
treatment
of
AD.13
BDPP
(bioac5ve
dietary
polyphenol
prepara5on)
A
combina5on
of
three
bioac5ve
and
commercially
available
polyphenol
products
including
Concord
grape
juice,
grape
seed
extract
and
resveratrol.14
It
was
created
to
simultaneously
affect
mul5ple
Alzheimer’s
targets
such
as
amyloid
load,
synap5c
plas5city
and
cogni5on.14,
1
Piceatannol
The
compound
trans-­‐3,4,3ʹ′,5ʹ′-­‐tetrahydroxys5lbene,
which
has
a
structure
homologous
to
resveratrol.
It
is
an
an5-­‐inflammatory
s5lbene
derived
from
the
seeds
of
Euphorbia
lagascae.15
It
may
block
Aβ
-­‐induced
accumula5on
of
reac5ve
oxygen
species,
which
ul5mately
leads
to
neuronal
cell
death.6
Figure
1:
Res
ac5on
in
inhibi5ng
β-­‐amyloid
plaque
forma5on
Image Adapted from Patterson, C. et al.
Conclusions
We wish to thank Aaron Magnuson, James Peth, and Dr. Cunningham-Sabo for their advisement in the
development of this poster.
Research
proves
Res’s
low
bioavailability
due
to
it’s
rapid
metabolism
by
the
liver.8
To
enhance
bioavailability,
related
compounds
have
been
found
and
synthe5cs
have
been
created11,
12,
13,
14,
1,
15,
6
Acknowledgements
Table
1:
Similar
Compounds/Synthe5cs
Image by Susan Landau and William Jagust