Grant Detail

The grant detail shows the name of the PI, active dates of the project, the funding institute and the abstract of the grant. This abstract is what is used to create the fingerprint of the grant. If any publications referencing this grant are found in the data, they will be listed here as well.

Can Omega 3 fatty acids Slow Alzheimer Pathogensis?

Cole, Greg M

1 September 2005 - 31 August 2009
NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE
Total Funding: $ 1,072,290

Alzheimer's Disease (AD) risk is reduced by fish consumption, possibly due to long chain omega 3 fatty acids (eicospentaenoic acid (EPA) and docosahexaenoic acid (DHA). Lab chows typically contain abundant soy and fish and are omega-3 fatty acids sufficient raising the issue of whether omega 3 in the chow influences AD pathogenesis in lab models. Aged APPsw AD model mice were placed on a DHA-depleting "Bad" diet with safflower oil as the principal fat. With no evidence for neuron or synaptophysin loss, DHA depletion increased oxidative damage, caspase-cleaved actin and deficits in PSD-95 and the dendritic spine actin-binding protein, drebrin. The effect was transgene-dependent, suggesting that the "Bad" diet is permissive for a selective APP transgene-induced post-synaptic deficit. Only Tg(+) mice on "Bad" diet developed major deficits in mRNA and protein associated with postsynaptic function and memory, including neuroprotective principal investigator3K p85 that regulates both caspase and tau kinase activation. Whether dietary DHA's neuroprotective effects come from regulation of phosphatidylserine levels and principal investigator3-K or from lipoxygenase derived DHA metabolites (neuroprotectin Dl) remains unknown. Amyloid pathology was also reduced by DHA supplementation, but the mechanisms involved also remain unclear: DHA did not induce transthyretin (TTR), an anti-amyloid protein that reduces AD pathology and has been reportedly induced by fish oil. Currently fish oil supplementation is a relatively safe and cheap alternative to either increased fish consumption with risks of mercury and lipid soluble toxins or more expensive algae-derived DHA supplementation. We hypothesize that: 1) Fish oil supplementation will synergize with the antioxidant curcumin and work as well or better than DHA in our AD model in controlling synaptic marker loss. 2) Fish oil will have similar anti-amyloid activities as DHA, but also induce TTR and be more effective in controlling amyloid. 3) EPA supplementation will induce only a subset of the protective effects of DHA. 4) Fish oil or DHA will increase principal investigator3-K pathway inhibition of GSK36 and tau pathology. We propose to test these hypotheses in transgenic and culture models with and without baseline omega-3 depletion providing more information on mechanism, active ingredient and the utility of marine oil and antioxidant supplementation relevant to the prevention and treatment of Alzheimer's disease.

8 Resulting Publications

• 1.

  2010

  Greg M Cole; Qiu-Lan Ma; Sally A Frautschy

  Dietary fatty acids and the aging brain.

  Nutrition reviews 2010;68 Suppl 2():S102-11.

• 2.

  2010

  Greg M Cole; Sally A Frautschy

  DHA may prevent age-related dementia.

  The Journal of nutrition 2010;140(4):869-74.

• 3.

  2009

  Greg M Cole; Qiu-Lan Ma; Sally A Frautschy

  Omega-3 fatty acids and dementia.

  Prostaglandins, leukotrienes, and essential fatty acids 2009;81(2-3):213-21.

• 4.

  2009

  Qiu-Lan Ma; Fusheng Yang; Emily R Rosario; Oliver J Ubeda; Walter Beech; Dana J Gant; Ping Ping Chen; Beverly Hudspeth; Cory Chen; Yongle 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.

  The Journal of neuroscience : the official journal of the Society for Neuroscience 2009;29(28):9078-89.

• 5.

  2009

  Qiu-Lan Ma; Douglas R Galasko; John M Ringman; Harry V Vinters; Steven D Edland; Justine Pomakian; Oliver J Ubeda; Emily R Rosario; Bruce Teter; Sally A Frautschy; et al.

  Reduction of SorLA/LR11, a sorting protein limiting beta-amyloid production, in Alzheimer disease cerebrospinal fluid.

  Archives of neurology 2009;66(4):448-57.

• 6.

  2008

  Qiu-Lan Ma; Fusheng Yang; Frédéric Calon; Oliver J Ubeda; James E Hansen; Richard H Weisbart; Walter Beech; Sally A Frautschy; Greg M Cole

  p21-activated kinase-aberrant activation and translocation in Alzheimer disease pathogenesis.

  The Journal of biological chemistry 2008;283(20):14132-43.

• 7.

  2007

  Qiu-Lan Ma; Bruce Teter; Oliver J Ubeda; Takashi Morihara; Dilsher Dhoot; Michael D Nyby; Michael L Tuck; Sally A Frautschy; Greg 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.

  The Journal of neuroscience : the official journal of the Society for Neuroscience 2007;27(52):14299-307.

• 8.

  2007

  Greg M Cole; Sally A Frautschy

  The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer's Disease.

  Experimental gerontology 2007;42(1-2):10-21.

Scientific Context

This section shows information that has been computed by using the fingerprint of the grant, including related publications, related experts and related grants - all with fingerprints representing significant amounts of overlap between their fingerprint and this grant. The red dots indicate whether those experts or terms actually appear within this grant, showing potential and actual connections.