WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, March 23, 2005, 25(12):3032-3040; doi:10.1523/JNEUROSCI.4225-04.2005

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (132)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lim, G. P.
Right arrow Articles by Cole, G. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lim, G. P.
Right arrow Articles by Cole, G. M.

 Previous Article  |  Next Article 

Neurobiology of Disease
A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model

Giselle P. Lim,1,3 Frédéric Calon,1,3 Takashi Morihara,1,3 Fusheng Yang,1,3 Bruce Teter,1,3 Oliver Ubeda,1,3 Norman Salem, Jr,5 Sally A. Frautschy,1,3,2,4 and Greg M. Cole1,3,2,4

Departments of 1Medicine and 2Neurology, University of California Los Angeles, Los Angeles, California 90095, 3Veterans Affairs Greater Los Angeles Healthcare System and 4Geriatric Research Educational Clinical Center, North Hills, California 91343, and 5Section of Nutritional Neuroscience, Laboratory of Membrane Biochemistry and Biophysics, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852

Epidemiological studies suggest that increased intake of the omega-3 (n-3) polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with reduced risk of Alzheimer's disease (AD). DHA levels are lower in serum and brains of AD patients, which could result from low dietary intake and/or PUFA oxidation. Because effects of DHA on Alzheimer pathogenesis, particularly on amyloidosis, are unknown, we used the APPsw (Tg2576) transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden. Aged animals (17-19 months old) were placed in one of three groups until 22.5 months of age: control (0.09% DHA), low-DHA (0%), or high-DHA (0.6%) chow. {beta}-Amyloid (A{beta}) ELISA of the detergent-insoluble extract of cortical homogenates showed that DHA-enriched diets significantly reduced total A{beta} by >70% when compared with low-DHA or control chow diets. Dietary DHA also decreased A{beta}42 levels below those seen with control chow. Image analysis of brain sections with an antibody against A{beta} (amino acids 1-13) revealed that overall plaque burden was significantly reduced by 40.3%, with the largest reductions (40-50%) in the hippocampus and parietal cortex. DHA modulated APP processing by decreasing both {alpha}- and {beta}-APP C-terminal fragment products and full-length APP. BACE1 ({beta}-secretase activity of the {beta}-site APP-cleaving enzyme), ApoE (apolipoprotein E), and transthyretin gene expression were unchanged with the high-DHA diet. Together, these results suggest that dietary DHA could be protective against {beta}-amyloid production, accumulation, and potential downstream toxicity.

Key words: DHA; polyunsaturated fatty acid; A{beta}; APP; secretase; Alzheimer

Received Oct 11, 2004; revised February 8, 2005; accepted February 9, 2005.




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
J. Joseph, G. Cole, E. Head, and D. Ingram
Nutrition, Brain Aging, and Neurodegeneration
J. Neurosci., October 14, 2009; 29(41): 12795 - 12801.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Q.-L. Ma, F. Yang, E. R. Rosario, O. J. Ubeda, W. Beech, D. J. Gant, P. P. Chen, B. Hudspeth, C. Chen, Y. Zhao, et al.
{beta}-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin
J. Neurosci., July 15, 2009; 29(28): 9078 - 9089.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
J. W. Fetterman Jr. and M. M. Zdanowicz
Therapeutic potential of n-3 polyunsaturated fatty acids in disease
Am. J. Health Syst. Pharm., July 1, 2009; 66(13): 1169 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 J Gerontol A Biol Sci Med SciHome page
M. Umezawa, K. Higuchi, M. Mori, T. Matushita, and M. Hosokawa
Effect of Dietary Unsaturated Fatty Acids on Senile Amyloidosis in Senescence-Accelerated Mice
J Gerontol A Biol Sci Med Sci, June 1, 2009; 64A(6): 646 - 652.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
W. S. Harris, D. Mozaffarian, M. Lefevre, C. D. Toner, J. Colombo, S. C. Cunnane, J. M. Holden, D. M. Klurfeld, M. C. Morris, and J. Whelan
Towards Establishing Dietary Reference Intakes for Eicosapentaenoic and Docosahexaenoic Acids
J. Nutr., April 1, 2009; 139(4): 804S - 819S.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. Torres-Aleman
Mouse Models of Alzheimer's Dementia: Current Concepts and New Trends
Endocrinology, December 1, 2008; 149(12): 5952 - 5957.
[Abstract] [Full Text] [PDF]

Home page
 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
A. L. Petursdottir, S. A. Farr, J. E. Morley, W. A. Banks, and G. V. Skuladottir
Effect of Dietary n-3 Polyunsaturated Fatty Acids on Brain Lipid Fatty Acid Composition, Learning Ability, and Memory of Senescence-Accelerated Mouse
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2008; 63(11): 1153 - 1160.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Delbosc, M. Glorian, A.-S. Le Port, G. Bereziat, M. Andreani, and I. Limon
The Benefit of Docosahexanoic Acid on the Migration of Vascular Smooth Muscle Cells Is Partially Dependent on Notch Regulation of MMP-2/-9
Am. J. Pathol., May 1, 2008; 172(5): 1430 - 1440.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. Bousquet, M. Saint-Pierre, C. Julien, N. Salem Jr., F. Cicchetti, and F. Calon
Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson's disease
FASEB J, April 1, 2008; 22(4): 1213 - 1225.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
Z. Ungvari, C. Parrado-Fernandez, A. Csiszar, and R. de Cabo
Mechanisms Underlying Caloric Restriction and Lifespan Regulation: Implications for Vascular Aging
Circ. Res., March 14, 2008; 102(5): 519 - 528.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Q.-L. Ma, B. Teter, O. J. Ubeda, T. Morihara, D. Dhoot, M. D. Nyby, M. L. Tuck, S. A. Frautschy, and G. M. Cole
Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention
J. Neurosci., December 26, 2007; 27(52): 14299 - 14307.
[Abstract] [Full Text] [PDF]

Home page
 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
A. Cherubini, C. Andres-Lacueva, A. Martin, F. Lauretani, A. D. Iorio, B. Bartali, A. Corsi, S. Bandinelli, M. P. Mattson, and L. Ferrucci
Low Plasma N-3 Fatty Acids and Dementia in Older Persons: The InCHIANTI Study
J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2007; 62(10): 1120 - 1126.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. N. Green, H. Martinez-Coria, H. Khashwji, E. B. Hall, K. A. Yurko-Mauro, L. Ellis, and F. M. LaFerla
Dietary Docosahexaenoic Acid and Docosapentaenoic Acid Ameliorate Amyloid-{beta} and Tau Pathology via a Mechanism Involving Presenilin 1 Levels
J. Neurosci., April 18, 2007; 27(16): 4385 - 4395.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
T. M. Malm, H. Iivonen, G. Goldsteins, V. Keksa-Goldsteine, T. Ahtoniemi, K. Kanninen, A. Salminen, S. Auriola, T. Van Groen, H. Tanila, et al.
Pyrrolidine Dithiocarbamate Activates Akt and Improves Spatial Learning in APP/PS1 Mice without Affecting {beta}-Amyloid Burden
J. Neurosci., April 4, 2007; 27(14): 3712 - 3721.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
M. C. Morris
Docosahexaenoic Acid and Alzheimer Disease
Arch Neurol, November 1, 2006; 63(11): 1527 - 1528.
[Full Text] [PDF]

Home page
 BrainHome page
C. L. Masters and K. Beyreuther
Alzheimer's centennial legacy: prospects for rational therapeutic intervention targeting the A{beta} amyloid pathway
Brain, November 1, 2006; 129(11): 2823 - 2839.
[Abstract] [Full Text] [PDF]

Home page
 Arch NeurolHome page
Y. Freund-Levi, M. Eriksdotter-Jonhagen, T. Cederholm, H. Basun, G. Faxen-Irving, A. Garlind, I. Vedin, B. Vessby, L.-O. Wahlund, and J. Palmblad
{omega}-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial.
Arch Neurol, October 1, 2006; 63(10): 1402 - 1408.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
V. Stenset, L. Johnsen, D. Kocot, A. Negaard, A. Skinningsrud, P. Gulbrandsen, A. Wallin, and T. Fladby
Associations between white matter lesions, cerebrovascular risk factors, and low CSF Abeta42.
Neurology, September 12, 2006; 67(5): 830 - 833.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
A. A. Farooqui and L. A. Horrocks
Phospholipase A2-Generated Lipid Mediators in the Brain: The Good, the Bad, and the Ugly
Neuroscientist, June 1, 2006; 12(3): 245 - 260.
[Abstract] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
L. M Arterburn, E. B. Hall, and H. Oken
Distribution, interconversion, and dose response of n-3 fatty acids in humans
Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1467 - 1476S.
[Abstract] [Full Text] [PDF]

Home page
 CMAJHome page
F. Calon
Nonpatentable drugs and the cost of our ignorance.
Can. Med. Assoc. J., February 14, 2006; 174(4): 483 - 484.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
C. N. Serhan, K. Gotlinger, S. Hong, Y. Lu, J. Siegelman, T. Baer, R. Yang, S. P. Colgan, and N. A. Petasis
Anti-Inflammatory Actions of Neuroprotectin D1/Protectin D1 and Its Natural Stereoisomers: Assignments of Dihydroxy-Containing Docosatrienes
J. Immunol., February 1, 2006; 176(3): 1848 - 1859.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. T. Maloney, L. S. Minamide, A. W. Kinley, J. A. Boyle, and J. R. Bamburg
{beta}-Secretase-Cleaved Amyloid Precursor Protein Accumulates at Actin Inclusions Induced in Neurons by Stress or Amyloid {beta}: A Feedforward Mechanism for Alzheimer's Disease
J. Neurosci., December 7, 2005; 25(49): 11313 - 11321.
[Abstract] [Full Text] [PDF]


-
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-