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The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.
Alzheimers Res Ther. 2016 06 30; 8:25.AR

Abstract

BACKGROUND

Apolipoprotein E (APOE) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer's disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our objective in the present study was to examine whether APOE ɛ4 genotype and low CSF Aβ42 levels were associated with reduced delivery of DHA to CSF in the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial.

METHODS

Phospholipid DHA was assayed in the plasma of 384 participants and CSF of 70 participants at baseline. Forty-four of the 70 participants completed the 18-month follow-up visit after allocation to placebo (n = 15) or DHA (n = 29). Plasma and CSF DHA levels, CSF Aβ42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline Aβ42 CSF levels. To assess DHA delivery across the blood-brain barrier, the ratio of CSF to plasma DHA levels was calculated.

RESULTS

At baseline, there were no significant differences between CSF or plasma phospholipid DHA levels by CSF Aβ42 tertiles or ɛ4 status. After 18 months of DHA supplementation, participants at the lowest Aβ42 tertile had significantly lower CSF DHA levels (p = 0.01) and lower CSF-to-plasma DHA ratios (p = 0.05) compared to the other tertiles. Baseline CSF Aβ42 levels were significantly lower in ɛ4 carriers than in ɛ4 noncarriers (p = 0.01). Participants carrying the ɛ4 allele (n = 25) demonstrated a less pronounced increase in CSF DHA level compared with noncarriers (n = 4), with a possible interaction effect between treatment and APOE genotype (p = 0.07).

CONCLUSIONS

APOE ɛ4 allele and lower CSF Aβ42 levels were associated with less transport of DHA to CSF. Brain amyloid pathology may limit the delivery of DHA to the brain in AD.

TRIAL REGISTRATION

Clinicaltrials.gov identifier: NCT00440050 . Registered on 22 Feb 2007.

Links

PMC Free PDF

Authors+Show Affiliations

Yassine HN
Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. hyassine@usc.edu.
Rawat V
Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Mack WJ
Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Quinn JF
Department of Neurology, Oregon Health & Science University, and Portland VA Medical Center , Portland, OR, USA.
Yurko-Mauro K
Clinical Research Department, DSM Nutritional Products, Columbia, MD, USA.
Bailey-Hall E
Clinical Research Department, DSM Nutritional Products, Columbia, MD, USA.
Aisen PS
Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Chui HC
Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Schneider LS
Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, USA.

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesApolipoprotein E4BiomarkersDietary SupplementsDocosahexaenoic AcidsDouble-Blind MethodFollow-Up StudiesGenotypeHumansPeptide FragmentsPhosphorylationtau Proteins

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27358067

Clinical Trial Links

Clinical trial which this article describes

Citation

Yassine, Hussein N., et al. "The Effect of APOE Genotype On the Delivery of DHA to Cerebrospinal Fluid in Alzheimer's Disease." Alzheimer's Research & Therapy, vol. 8, 2016, p. 25.
Yassine HN, Rawat V, Mack WJ, et al. The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. Alzheimers Res Ther. 2016;8:25.
Yassine, H. N., Rawat, V., Mack, W. J., Quinn, J. F., Yurko-Mauro, K., Bailey-Hall, E., Aisen, P. S., Chui, H. C., & Schneider, L. S. (2016). The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. Alzheimer's Research & Therapy, 8, 25. https://doi.org/10.1186/s13195-016-0194-x
Yassine HN, et al. The Effect of APOE Genotype On the Delivery of DHA to Cerebrospinal Fluid in Alzheimer's Disease. Alzheimers Res Ther. 2016 06 30;8:25. PubMed PMID: 27358067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. AU - Yassine,Hussein N, AU - Rawat,Varun, AU - Mack,Wendy J, AU - Quinn,Joseph F, AU - Yurko-Mauro,Karin, AU - Bailey-Hall,Eileen, AU - Aisen,Paul S, AU - Chui,Helena C, AU - Schneider,Lon S, Y1 - 2016/06/30/ PY - 2016/03/05/received PY - 2016/06/06/accepted PY - 2016/7/1/entrez PY - 2016/7/1/pubmed PY - 2017/10/17/medline KW - APOE KW - Alzheimer’s disease KW - Amyloid KW - Cerebrospinal fluid SP - 25 EP - 25 JF - Alzheimer's research & therapy JO - Alzheimers Res Ther VL - 8 N2 - BACKGROUND: Apolipoprotein E (APOE) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer's disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our objective in the present study was to examine whether APOE ɛ4 genotype and low CSF Aβ42 levels were associated with reduced delivery of DHA to CSF in the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial. METHODS: Phospholipid DHA was assayed in the plasma of 384 participants and CSF of 70 participants at baseline. Forty-four of the 70 participants completed the 18-month follow-up visit after allocation to placebo (n = 15) or DHA (n = 29). Plasma and CSF DHA levels, CSF Aβ42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline Aβ42 CSF levels. To assess DHA delivery across the blood-brain barrier, the ratio of CSF to plasma DHA levels was calculated. RESULTS: At baseline, there were no significant differences between CSF or plasma phospholipid DHA levels by CSF Aβ42 tertiles or ɛ4 status. After 18 months of DHA supplementation, participants at the lowest Aβ42 tertile had significantly lower CSF DHA levels (p = 0.01) and lower CSF-to-plasma DHA ratios (p = 0.05) compared to the other tertiles. Baseline CSF Aβ42 levels were significantly lower in ɛ4 carriers than in ɛ4 noncarriers (p = 0.01). Participants carrying the ɛ4 allele (n = 25) demonstrated a less pronounced increase in CSF DHA level compared with noncarriers (n = 4), with a possible interaction effect between treatment and APOE genotype (p = 0.07). CONCLUSIONS: APOE ɛ4 allele and lower CSF Aβ42 levels were associated with less transport of DHA to CSF. Brain amyloid pathology may limit the delivery of DHA to the brain in AD. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00440050 . Registered on 22 Feb 2007. SN - 1758-9193 UR - https://www.unboundmedicine.com/medline/citation/27358067/The_effect_of_APOE_genotype_on_the_delivery_of_DHA_to_cerebrospinal_fluid_in_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -