FISH OIL / OMEGA-3 / PUFA AND ALZHEIMERS

acrolein and HNE are a lipid peroxide/breakdown products from the consumption of PUFAs, mainly DHA and EPA which are the primary omega-3's in fish oil. (source: http://www.ncbi.nlm.nih.gov/pubmed/11896684/)

acrolein has been implicated along with t-4-hydroxy-2-nonenal (HNE) and other markers of PUFA peroxidation in alzheimer's plus other degenerative brain disorders:

"In Alzheimer’s disease (AD) brain increased lipid peroxidation and decreased energy utilization are found. Mitochondria membranes contain a significant amount of arachidonic and linoleic acids, precursors of lipid peroxidation products, 4-hydroxynonenal (HNE) and 2-propen-1-al (acrolein), that are extremely reactive.  [...] Acrolein, which is increased in AD brain, may be partially responsible for the dysfunction of mitochondria and loss of energy found in AD brain by inhibition of PDH and KGDH activities, potentially contributing to the neurodegeneration in this disorder." http://www.ncbi.nlm.nih.gov/pubmed/14715435

"In hippocampal neuron cultures, acrolein was neurotoxic in a time- and concentration-dependent manner and more toxic than HNE at 5 microM concentrations of each. Acrolein exposure led to a significant concentration-dependent increase in intracellular calcium concentrations. Collectively, these data show that acrolein is increased in the brain in AD and demonstrate neurotoxicity mechanisms that might be important in the pathogenesis of neuron degeneration in AD." http://www.ncbi.nlm.nih.gov/pubmed/11182468

"Previous studies show increased levels of lipid peroxidation and neurotoxic by-products of lipid peroxidation including 4-hydroxynonenal (HNE) and acrolein in vulnerable regions of the Alzheimer’s disease (AD) brain. [...] Our data show that there is a statistically significant (P<0.05) increase in HNE in HPG, SMTG and CER in MCI compared to age-matched control subjects. Specimens of SMTG also showed a significant increase in levels of acrolein in MCI. Comparison of EAD and control subjects showed a statistically significant increase in HNE in HPG and SMTG and a significant increase in acrolein in all three brain regions studied. [...] These results suggest that lipid peroxidation occurs early in the pathogenesis of AD." http://www.ncbi.nlm.nih.gov/pubmed/15993986

"Early Alzheimer’s disease (EAD) is the intermediary stage between mild cognitive impairment (MCI) and late-stage Alzheimer’s disease (AD). [...] Oxidative stress in brain is reported in MCI and AD, including lipid peroxidation indexed by protein-bound 4-hydroxy-2-nonenal (HNE) [...] The results are consistent with the hypothesis that oxidative stress, in particular lipid peroxidation, is an early event in the progression of AD, and is the first to identify in EAD identical brain proteins previously identified as HNE-modified in MCI and late-state AD." http://www.ncbi.nlm.nih.gov/pubmed/19374891

"Oxidative stress has been implicated in the pathogenesis of Alzheimer’s disease (AD). Both AD and arguably its earlier form, mild cognitive impairment (MCI), have elevated membrane oxidative damage in brain. [...] By immunoprecipitation assay, we also investigated whether 4-hydroxy-2-transnonenal (HNE), an aldehydic product of lipid peroxidation, was bound in excess to p53 in IPL from subjects with MCI and AD compared to control. Overall, the data provide evidence that p53 is involved in the neuronal death in both MCI and AD, suggesting that the observed alterations are early events in the progression of AD. In addition, HNE may be a novel non-protein mediator of oxidative stress-induced neuronal apoptosis." http://www.ncbi.nlm.nih.gov/pubmed/18494939

"The largest number of studies have been performed in Alzheimer’s disease (AD) where there is considerable support for the oxidative stress hypothesis in the pathogenesis of neuron degeneration. In autopsied brain there is an increase in lipid peroxidation, a decline in polyunsaturated fatty acids (PUFA) and an increase in 4-hydroxynonenal (HNE), a neurotoxic aldehyde product of PUFA oxidation [...] Overall these studies indicate that oxidative stress and the inflammatory cascade, working in concert, are important in the pathogenetic cascade of neurodegeneration in AD, suggesting that therapeutic efforts aimed at both of these mechanisms may be beneficial." http://www.ncbi.nlm.nih.gov/pubmed/9989456

"Oxidative stress has been implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer’s disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE), F2-isoprostanes, and F4-neuroprostanes are present in the brain in patients with AD. Acrolein, an α,β-unsaturated aldehydic product of lipid peroxidation has been demonstrated to be approximately 100 times more reactive than HNE and is present in neurofibrillary tangles in the brain in AD [...] Concentrations of acrolein were two to five times those of HNE in the same samples. [...] acrolein causes a concentration-dependent impairment of glutamate uptake and glucose transport in cortical neuron cultures. [...] Collectively, these data demonstrate neurotoxicity mechanisms of arolein that might be important in the pathogenesis of neuron degeneration in AD."
http://www.sciencedirect.com/.../pii/S0891584900003464

 "Abeta induces lipid peroxidation in ways that are inhibited by free radical antioxidants. Two reactive products of lipid peroxidation are the alkenals, 4-hydroxynonenal (HNE) and 2-propenal (acrolein). [...] These results are consistent with the notion of a coupling of the oxidative environment in AD brain and increased risk of developing this disorder. Taken together, the findings from in-vitro studies of lipid peroxidation induced by Abeta(1-42) and postmortem studies of lipid peroxidation (and its sequelae) in AD brain may help explain the APOE allele-related risk for AD, some of the functional and structural alterations in AD brain, and strongly support a causative role of Abeta(1-42)-induced oxidative stress in AD neurodegeneration."
http://www.ncbi.nlm.nih.gov/pubmed/12392766

"Alzheimer’s Disease (AD) is a clinical-pathological entity that probably derives from different causes. Mounting evidence strongly implicates regionally increased oxidative damage to brain beyond what occurs with aging as one of the processes that may contribute to AD progression. While several different classes of molecules may be affected, lipid peroxidation is thought to be a prominent and especially deleterious form of oxidative damage in brain due to this organ’s relative enrichment in polyunsaturated fatty acids."
http://www.ncbi.nlm.nih.gov/pubmed/12679837





"F2-isoprostanes are prostaglandin F2-like compounds that are formed nonenzymatically by free radical-induced oxidation of arachidonic acid. We explored whether oxidation of docosahexaenoic acid (C22:6omega3), which is highly enriched in the brain, led to the formation of F2-isoprostane-like compounds, which we term F4-neuroprostanes. [...] F4-neuroprostanes could be detected in normal human cerebrospinal fluid and levels in patients with Alzheimer’s disease (110 +/- 12 pg/ml) were significantly higher than age-matched controls (64 +/- 8 pg/ml) (p < 0.05). F4-neuroprostanes may provide a unique marker of oxidative injury to the brain and could potentially exert biological activity. Furthermore, the formation of F4-neuroprostane-containing aminophospholipids might adversely effect neuronal function as a result of alterations they induce in the biophysical properties of neuronal membranes."
http://www.ncbi.nlm.nih.gov/pubmed/9593698


"It has been suggested that the dietary intake of omega-3 polyunsaturated fatty acids could be inversely related to the risk of dementia and cognitive decline. This analysis examined the association between plasma concentration of omega-3 polyunsaturated fatty acids and prevalence and incidence of cognitive impairment and dementia. [...] In the prospective analysis, a higher eicosapentaenoic acid (p < 0.01) concentration was found in cognitively impaired cases compared to controls while higher docosahexaenoic acid (p < 0.07), omega-3 (p < 0.04) and total polyunsaturated fatty acid (p < 0.03) concentrations were found in dementia cases. These findings do not support the hypothesis that omega-3 polyunsaturated fatty acids play a protective role in cognitive function and dementia." http://www.ncbi.nlm.nih.gov/pubmed/14624027


also remember, women have higher rates of alzheimers, and also have more severe symptoms on average....

"Here we determined erythrocyte and regional brain docosahexaenoic acid (DHA, 22:6n-3) composition in intact male and female rats, and in chronically ovariectomized (OVX) rats with or without cyclic estradiol treatment (2 microg/4d). All groups were maintained on diets with or without the DHA precursor alpha-linolenic acid (ALA, 18:3n-3). We report that both male (-21%) and OVX (-19%) rats on ALA+ diet exhibited significantly lower erythrocyte DHA composition relative to female controls. [...] These preclinical data corroborate clinical evidence for gender differences in peripheral DHA composition (female>male), demonstrate gender differences in PFC DHA composition (male>female), and support a link between ovarian hormones and erythrocyte and region-specific brain DHA composition." http://www.ncbi.nlm.nih.gov/pubmed/19046819