title: Alterations in erythrocyte fatty acid composition in preclinical Alzheimer's disease.
abstract: Brain and blood fatty acids (FA) are altered in Alzheimer's disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65-90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand18F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio; SUVR < 1.35, N = 65) and high NAL or preclinical AD (SUVR ≥ 1.35, N = 35) wherein, linear models were employed to compare FA compositions between the two groups. Increased arachidonic acid (AA, p < 0.05) and decreased docosapentaenoic acid (DPA, p < 0.05) were observed in high NAL. To differentiate low from high NAL, the area under the curve (AUC) generated from a 'base model' comprising age, gender, APOEε4 and education (AUC = 0.794) was outperformed by base model + AA:DPA (AUC = 0.836). Our findings suggest that specific alterations in erythrocyte FA composition occur very early in the disease pathogenic trajectory, prior to cognitive impairment. As erythrocyte FA levels are reflective of tissue FA, these alterations may provide insight into the pathogenic mechanism(s) of the disease and may highlight potential early diagnostic markers and therapeutic targets.
authors.affiliation: Anglicare, Sydney, NSW, Australia.|School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia.|School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.|Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.|KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia.|McCusker Alzheimer Research Foundation, Nedlands, WA, Australia.|The Cooperative Research Centre for Mental Health, Carlton, VIC, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Goozee
authors.affiliation: School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.|Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.|KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia.
authors.forename: Pratishtha
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, WA, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.affiliation: School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.|McCusker Alzheimer Research Foundation, Nedlands, WA, Australia.|Australian eHealth Research Centre, CSIRO, Australia.
authors.forename: Kaikai
authors.initials: K
authors.lastname: Shen
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia.|School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.|Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.|McCusker Alzheimer Research Foundation, Nedlands, WA, Australia.|The Cooperative Research Centre for Mental Health, Carlton, VIC, Australia.
authors.forename: Hamid R
authors.identifier: http://orcid.org/0000-0001-8017-8682
authors.initials: HR
authors.lastname: Sohrabi
authors.affiliation: KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia.|School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia.
authors.forename: Prita R
authors.initials: PR
authors.lastname: Asih
authors.affiliation: Anglicare, Sydney, NSW, Australia.
authors.forename: Preeti
authors.initials: P
authors.lastname: Dave
authors.affiliation: KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia.
authors.forename: Bethany
authors.initials: B
authors.lastname: Ball
authors.affiliation: Anglicare, Sydney, NSW, Australia.
authors.forename: Candice
authors.initials: C
authors.lastname: ManYan
authors.affiliation: School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.|McCusker Alzheimer Research Foundation, Nedlands, WA, Australia.|The Cooperative Research Centre for Mental Health, Carlton, VIC, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Taddei
authors.affiliation: Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Chung
authors.affiliation: Nutraceuticals Research Program, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
authors.forename: Manohar L
authors.initials: ML
authors.lastname: Garg
authors.affiliation: School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, Australia. r.martins@ecu.edu.au.|School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia. r.martins@ecu.edu.au.|Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia. r.martins@ecu.edu.au.|KaRa Institute of Neurological Diseases, Macquarie Park, NSW, Australia. r.martins@ecu.edu.au.|McCusker Alzheimer Research Foundation, Nedlands, WA, Australia. r.martins@ecu.edu.au.|The Cooperative Research Centre for Mental Health, Carlton, VIC, Australia. r.martins@ecu.edu.au.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D001921:Brain / Q000378:metabolism; D004041:Dietary Fats; D004912:Erythrocytes / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D066329:Protein Aggregates