uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Basun, H
Alternative names
Publications (10 of 36) Show all publications
Jernerén, F., Cederholm, T., Refsum, H., Smith, A. D., Turner, C., Palmblad, J., . . . Freund-Levi, Y. (2019). Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease: The OmegAD Study. Journal of Alzheimer's Disease, 69(1), 189-197
Open this publication in new window or tab >>Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease: The OmegAD Study
Show others...
2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, no 1, p. 189-197Article in journal (Refereed) Published
Abstract [en]

Background: Trials of supplementation with omega-3 fatty acids (omega 3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and omega 3-FAs in relation to brain atrophy and cognitive decline.

Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of omega 3-FAs supplementation on cognitive performance in moderate AD.

Methods: This post hoc analysis of the OmegAD trial included 171 community-based patients with AD (MMSE >= 15): 88 patients received daily doses of 1.7 g docosahexaenoic acid and 0.6 g eicosapentaenoic acid for 6 months. Treatment outcome on cognition was analyzed according to baseline levels of tHcy using a general linear model and ANCOVA.

Results: We found significant interactions between omega 3-FA supplementation and tHcy on cognition and clinical stage assessed by MMSE (p = 0.040), global CDR (p = 0.059), and CDRsob (p = 0.023), but not on ADAS-cog (p = 0.649). In patients with tHcy levels <11.7 mu mol/L, omega 3-FA supplementation improved cognitive performance as measured by MMSE (+7.1%, 95% CI: 0.59 to 13.7%, p = 0.033) and clinical status as measured by CDRsob (-22.3%, 95% CI: -5.8 to -38.7%, p = 0.009) compared with placebo.

Conclusion: The effect of omega 3-FA supplementation on MMSE and CDR appears to be influenced by baseline tHcy, suggesting that adequate B vitamin status is required to obtain beneficial effects of omega 3-FA on cognition.

Keywords
Alzheimer's disease, B vitamins, cognition, dementia, homocysteine, omega-3 fatty acids
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-384475 (URN)10.3233/JAD-181148 (DOI)000467519100017 ()30958356 (PubMedID)
Funder
The Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedThe Karolinska Institutet's Research FoundationStiftelsen Gamla TjänarinnorÅke Wiberg Foundation, M16-0251Swedish Nutrition Foundation (SNF)Gun och Bertil Stohnes StiftelseSwedish Society of Medicine
Available from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-11Bibliographically approved
Faxen-Irving, G., Falahati, F., Basun, H., Eriksdotter, M., Vedin, I., Wahlund, L.-O., . . . Freund-Levi, Y. (2018). Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?. Journal of Alzheimer's Disease, 61(2), 515-519
Open this publication in new window or tab >>Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?
Show others...
2018 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, no 2, p. 515-519Article in journal (Refereed) Published
Abstract [en]

Low tissue levels of the major marine ω3 fatty acids (FAs) DHA and EPA are found in Alzheimer’s disease (AD). We investigated if healthy proxies to AD patients have higher levels of these ω3 FAs. We observed lower levels of EPA and DHA in subcutaneous adipose tissue biopsies from 64 AD patients compared with 16 cognitively healthy proxies. No significant difference was observed when pairwise comparisons were made between a subset of 16 AD patients and their co-habiting proxies. Larger studies are needed to replicate these findings and to determine if they could depend on FA intake or differences in metabolism.

Keywords
Alzheimer's disease, cognition, cohabitants, DHA, EPA, omega 3 fatty acids, subcutaneous adipose tissue
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:uu:diva-343881 (URN)10.3233/JAD-170359 (DOI)000422844100004 ()29154271 (PubMedID)
Funder
Stockholm County CouncilStiftelsen Gamla TjänarinnorSwedish Society of MedicineThe Dementia Association - The National Association for the Rights of the Demented
Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2018-03-16Bibliographically approved
Abu Hamdeh, S., Rollman Waara, E., Möller, C., Söderberg, L., Basun, H., Alafuzoff, I., . . . Marklund, N. (2018). Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury. Brain Pathology, 28(4), 451-462
Open this publication in new window or tab >>Rapid amyloid-β oligomer and protofibril accumulation in traumatic brain injury
Show others...
2018 (English)In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 28, no 4, p. 451-462Article in journal (Refereed) Published
Abstract [en]

Deposition of amyloid-β (Aβ) is central to Alzheimer's disease (AD) pathogenesis and associated with progressive neurodegeneration in traumatic brain injury (TBI). We analyzed predisposing factors for Aβ deposition including monomeric Aβ40, Aβ42 and Aβ oligomers/protofibrils, Aβ species with pronounced neurotoxic properties, following human TBI. Highly selective ELISAs were used to analyze N-terminally intact and truncated Aβ40 and Aβ42, as well as Aβ oligomers/protofibrils, in human brain tissue, surgically resected from severe TBI patients (n = 12; mean age 49.5 ± 19 years) due to life-threatening brain swelling/hemorrhage within one week post-injury. The TBI tissues were compared to post-mortem AD brains (n = 5), to post-mortem tissue of neurologically intact (NI) subjects (n = 4) and to cortical biopsies obtained at surgery for idiopathic normal pressure hydrocephalus patients (iNPH; n = 4). The levels of Aβ40 and Aβ42 were not elevated by TBI. The levels of Aβ oligomers/protofibrils in TBI were similar to those in the significantly older AD patients and increased compared to NI and iNPH controls (P < 0.05). Moreover, TBI patients carrying the AD risk genotype Apolipoprotein E epsilon3/4 (APOE ε3/4; n = 4) had increased levels of Aβ oligomers/protofibrils (P < 0.05) and of both N-terminally intact and truncated Aβ42 (P < 0.05) compared to APOE ε3/4-negative TBI patients (n = 8). Neuropathological analysis showed insoluble Aβ aggregates (commonly referred to as Aβ plaques) in three TBI patients, all of whom were APOE ε3/4 carriers. We conclude that soluble intermediary Aβ aggregates form rapidly after TBI, especially among APOE ε3/4 carriers. Further research is needed to determine whether these aggregates aggravate the clinical short- and long-term outcome in TBI.

Keywords
Alzheimer's disease, amyloid β oligomers, amyloid-β, traumatic brain injury
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-341911 (URN)10.1111/bpa.12532 (DOI)000439749700001 ()28557010 (PubMedID)
Funder
The Swedish Brain FoundationSwedish Research CouncilSwedish Institute
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2018-02-15 Created: 2018-02-15 Last updated: 2019-07-03Bibliographically approved
Karimi, M., Vedin, I., Levi, Y. F., Basun, H., Irving, G. F., Eriksdotter, M., . . . Palmblad, J. (2017). DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study. American Journal of Clinical Nutrition, 106(4), 1157-1165
Open this publication in new window or tab >>DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study
Show others...
2017 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 4, p. 1157-1165Article in journal (Refereed) Published
Abstract [en]

Background: Dietary fish oils, rich in long-chain n-3 (omega-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration. However, the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation, which controls messenger RNA generation-are poorly described. Objective: We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes (PBLs) and the relation to plasma EPA and DHA concentrations in Alzheimer disease (AD) patients. Design: In the present study, DNA methylation in four 5'-cytosinephosphate- guanine-3' (CpG) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients (30 given the n-3 FA preparation and 33 given placebo) as an estimation of the global DNA methylation in blood cells. Patients originated from the randomized, double-blind, placebo-controlled OmegAD study, in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA (the n-3 FA group) or placebo daily for 6 mo. Results: At 6 mo, the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations (2.6-and 3.5-fold), as well as decreased methylation in 2 out of 4 CpG sites (P<0.05 for all), respectively. This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration (r = -0.25, P = 0.045; and r = -0.26, P = 0.041, respectively), but not to changes in plasma DHA concentration, and were not related to apolipoprotein E-4 allele frequency. Conclusion: Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs. Our data may be of importance in measuring various effects of marine oils, including gene expression, in patients with AD and in other patients taking n-3 FA supplements. This trial was registered at clinicaltrials.gov as NCT00211159.

Place, publisher, year, edition, pages
AMER SOC NUTRITION-ASN, 2017
Keywords
fish oil, DHA, EPA, DNA methylation, LINE-1, Alzheimer disease
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-337084 (URN)10.3945/ajcn.117.155648 (DOI)000412004300022 ()28855224 (PubMedID)
Available from: 2018-01-31 Created: 2018-01-31 Last updated: 2018-02-22Bibliographically approved
Almkvist, O., Rodriguez-Vieitez, E., Thordardottir, S., Amberla, K., Axelman, K., Basun, H., . . . Graff, C. (2017). Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease. Journal of the International Neuropsychological Society, 23(3), 195-203
Open this publication in new window or tab >>Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease
Show others...
2017 (English)In: Journal of the International Neuropsychological Society, ISSN 1355-6177, E-ISSN 1469-7661, Vol. 23, no 3, p. 195-203Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.

Place, publisher, year, edition, pages
CAMBRIDGE UNIV PRESS, 2017
Keywords
Autosomal-dominant, Alzheimer's disease, Mutation carrier, Cognition, Predictors, Age of onset
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-320865 (URN)10.1017/S1355617716001028 (DOI)000398488800001 ()28079014 (PubMedID)
Funder
The Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedStockholm County CouncilSwedish Research CouncilThe Karolinska Institutet's Research Foundation
Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2017-04-26Bibliographically approved
Gunnarsson, M. D., Ingelsson, M., Blennow, K., Basun, H., Lannfelt, L. & Kilander, L. (2016). High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer's disease. Alzheimer's Research & Therapy, 8, Article ID 22.
Open this publication in new window or tab >>High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer's disease
Show others...
2016 (English)In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 22Article in journal (Refereed) Published
Abstract [en]

Background: Increased concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau, as well as decreased amyloid-beta 42 peptide, are biomarkers of Alzheimer's disease (AD) pathology, but few studies have shown an association with AD progression rate. We hypothesized that high CSF tau, as a marker of ongoing neurodegeneration, would predict a more aggressive course of AD, using time to nursing home placement (NHP) as the main outcome. Methods: Our sample inlcuded 234 patients with mild cognitive impairment (MCI) due to AD (n = 134) or mild to moderate AD (n = 100) who underwent lumbar puncture at a memory clinic and were followed for 2-11 years (median 4.9 years). Results: Individuals with CSF t-tau in the highest quartile (>= 900 ng/L) had a higher ratio of NHP, both in the total cohort and in patients with MCI only (adjusted HR 2.17 [95 % CI 1.24-3.80]; HR 2.37 [95 % CI 1.10-5.09], respectively), than the lowest quartile. The association between high t-tau levels and future steep deterioration was confirmed in analyses with conversion to moderate dementia (HR 1.66; 95 % CI 1.08-2.56), rapid decline in Mini Mental State Examination score (>= 4-point drop/12 months), and dying in severe dementia as outcomes. Conclusions: To our knowledge, this is the first study to show that high CSF t-tau levels predict early NHP and conversion to moderate dementia in an AD cohort. Selecting patients with high CSF t-tau, indicating more aggressive neurodegeneration and steeper decline, for AD immunotherapy trials might increase the possibility of showing contrast between active treatment and placebo.

Keywords
Nursing home placement, NHP, Alzheimer's disease, CSF, Tau, p-tau, Amyloid-beta, Rapid decline, Moderate dementia, Death in severe dementia
National Category
Nursing Geriatrics
Identifiers
urn:nbn:se:uu:diva-298845 (URN)10.1186/s13195-016-0191-0 (DOI)000376959600001 ()
Available from: 2016-07-11 Created: 2016-07-11 Last updated: 2019-05-09Bibliographically approved
Logovinsky, V., Satlin, A., Lai, R., Swanson, C., Kaplow, J., Osswald, G., . . . Lannfelt, L. (2016). Safety and tolerability of BAN2401 - a clinical study in Alzheimer's disease with a protofibril selective A beta antibody. Alzheimer's Research & Therapy, 8, Article ID 14.
Open this publication in new window or tab >>Safety and tolerability of BAN2401 - a clinical study in Alzheimer's disease with a protofibril selective A beta antibody
Show others...
2016 (English)In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 14Article in journal (Refereed) Published
Abstract [en]

Background: Several monoclonal antibodies for the treatment of Alzheimer's disease (AD) have been in development over the last decade. BAN2401 is a monoclonal antibody that selectively binds soluble amyloid beta (A beta) protofibrils.

Methods: Here we describe the first clinical study with BAN2401. Safety and tolerability were investigated in mild to moderate AD. A study design was used with staggered parallel single and multiple ascending doses, from 0.1 mg/kg as a single dose to 10 mg/kg biweekly for four months. The presence of amyloid related imaging abnormalities (ARIA, E for edema, H for hemorrhage) was assessed with magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) and plasma samples were analyzed to investigate pharmacokinetics (PK) and effects on biomarkers.

Results: The incidence of ARIA-E/H on MRI was comparable to that of placebo. BAN2401 exposure was approximately dose proportional, with a serum terminal elimination half-life of similar to 7 days. Only a slight increase of plasma A beta((1-40)) was observed but there were no measurable effects of BAN2401 on CSF biomarkers. On the basis of these findings Phase 2b efficacy study has been initiated in early AD.

Conclusions: BAN2401 was well-tolerated across all doses. The PK profile has guided us for selecting dose and dose regimens in the ongoing phase 2b study. There was no clear guidance for an effective dose based on biomarkers.

Keywords
Alzheimer's disease, Amyloid-beta, A beta, Protofibril, Immunotherapy, BAN2401, mAb158, ARIA, Clinical trial
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-294671 (URN)10.1186/s13195-016-0181-2 (DOI)000373482700001 ()27048170 (PubMedID)
Available from: 2016-06-01 Created: 2016-05-26 Last updated: 2019-05-09Bibliographically approved
Matsunaga, S., Kishi, T., Annas, P., Basun, H., Hampel, H. & Iwata, N. (2015). Lithium as a Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis. Journal of Alzheimer's Disease, 48(2), 403-410
Open this publication in new window or tab >>Lithium as a Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis
Show others...
2015 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 48, no 2, p. 403-410Article, review/survey (Refereed) Published
Abstract [en]

Background: This is the first meta-analysis of randomized placebo-controlled trials testing lithium as a treatment for patients with Alzheimer's disease (AD) and individuals with mild cognitive impairment (MCI). Methods: The primary outcome measure was efficacy on cognitive performance as measured through the Alzheimer's Disease Assessment Scale cognitive subscale or the Mini-Mental State Examination. Other outcome measures were drug discontinuation rate, individual side effects, and biological markers (phosphorylated tau 181, total tau, and amyloid-beta(42)) in cerebrospinal fluid (CSF). Results: Three clinical trials including 232 participants that met the study's inclusion criteria were identified. Lithium significantly decreased cognitive decline as compared to placebo (standardized mean difference = -0.41, 95% confidence interval = -0.81 to -0.02, p = 0.04, I-2 = 47%, 3 studies, n = 199). There were no significant differences in the rate of attrition, discontinuation due to all causes or adverse events, or CSF biomarkers between treatment groups. Conclusions: The results indicate that lithium treatment may have beneficial effects on cognitive performance in subjects with MCI and AD dementia.

Keywords
Alzheimer's disease, lithium, meta-analysis, mild cognitive impairment, systematic review
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-265967 (URN)10.3233/JAD-150437 (DOI)000361066200009 ()26402004 (PubMedID)
Available from: 2015-11-04 Created: 2015-11-04 Last updated: 2018-01-10Bibliographically approved
Eriksdotter, M., Vedin, I., Falahati, F., Freund-Levi, Y., Hjorth, E., Faxen-Irving, G., . . . Palmblad, J. (2015). Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD Study. Journal of Alzheimer's Disease, 48(3), 805-812
Open this publication in new window or tab >>Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD Study
Show others...
2015 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 48, no 3, p. 805-812Article in journal (Refereed) Published
Abstract [en]

Background: omega 3 fatty acids (omega 3 FAs) may slow the rate of decline in cognitive performance in mild forms of cognitive impairment and Alzheimer's disease (AD). However, the relationship between changes of plasma omega 3 FA levels and cognitive performance, as well as effects of gender, are poorly known. Objective: To study the effect of 6-month administration of DHA-rich omega 3 FA supplementation on plasma FA profiles in patients with mild to moderate AD in relation to cognitive performance and gender. This investigation is part of the OmegAD Study. Methods: 174 AD patients (74 +/- 9 years) were randomized to a daily intake of 2.3g omega 3 FA or placebo for 6 months; subsequently all received the omega 3 FA preparation for the next 6 months. Baseline as well as changes in plasma levels of the main omega 3 FAs in 165 patients, while receiving omega 3 FA supplementation for 6 months, were analyzed for association to cognitive performance (assessed by ADAS-cog and MMSE scores) as well as to gender. Results: Preservation of cognitive functioning, assessed by ADAS-cog or its sub-items (but not MMSE) scores, was significantly associated to increasing plasma omega 3 FA levels over time. Thus, the higher omega 3 FA plasma levels rose, the lower was the rate of cognitive deterioration. This effect was not related to gender; since although females displayed higher omega 3 FA plasma levels than did males after 6 months of supplementation, this difference disappeared when adjusted for body weight. Conclusions: Since our study suggests dose-response relationships between plasma levels of omega 3 FA and preservation of cognition, future omega 3 FA trials in patients with mild AD should consider exploring graded (and body weight adjusted) doses of omega 3 FA.

Keywords
Alzheimer's disease, cognition, DHA, EPA, gender, omega 3 fatty acids
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-267086 (URN)10.3233/JAD-150102 (DOI)000362958800022 ()26402079 (PubMedID)
Funder
Stockholm County Council
Available from: 2015-11-20 Created: 2015-11-17 Last updated: 2018-02-22
Freund-Levi, Y., Vedin, I., Hjorth, E., Basun, H., Irving, G. F., Schultzberg, M., . . . Basu, S. (2014). Effects of Supplementation with Omega-3 Fatty Acids on Oxidative Stress and Inflammation in Patients with Alzheimer's Disease: The OmegAD Study. Journal of Alzheimer's Disease, 42(3), 823-831
Open this publication in new window or tab >>Effects of Supplementation with Omega-3 Fatty Acids on Oxidative Stress and Inflammation in Patients with Alzheimer's Disease: The OmegAD Study
Show others...
2014 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 42, no 3, p. 823-831Article in journal (Refereed) Published
Abstract [en]

Background: Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (omega-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation. Objective: The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary omega-3 FA. Methods: Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F-2-isoprostane, 8-iso-PGF(2 alpha) a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF(2 alpha), a major metabolite of PGF(2 alpha) and biomarker of inflammatory response, were measured. Results: F-2-isoprostane in urine increased in the placebo group after 6 months, but therewas no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F-2-isoprostanes and 15-keto-dihydro-PGF(2 alpha). At baseline, the levels of 15-keto-dihydro-PGF(2 alpha) showed negative correlative relationships to omega-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF(2 alpha) correlated negatively to the omega-6 FA arachidonic acid. Conclusion: The findings indicate that supplementation of omega-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F-2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F-2 alpha. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.

Keywords
Alzheimer's disease, eicosanoids, F-2-isoprostane, inflammation, lipids, omega-3 fatty acids, oxidative stress, prostaglandin F-2 alpha
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-235525 (URN)10.3233/JAD-132042 (DOI)000342237000011 ()
Available from: 2014-11-05 Created: 2014-11-05 Last updated: 2018-02-22Bibliographically approved
Organisations

Search in DiVA

Show all publications