title: Buccal Cell Cytokeratin 14 Correlates with Multiple Blood Biomarkers of Alzheimer's Disease Risk.
abstract: Mild cognitive impairment (MCI) may reflect early stages of neurodegenerative disorders such as Alzheimer's disease (AD). Our hypothesis was that cytokeratin 14 (CK14) expression could be used with blood-based biomarkers such as homocysteine, vitamin B12, and folate to identify individuals with MCI or AD from the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging. Buccal cells from 54 individuals were analyzed by a newly developed method that is rapid, automated, and quantitative for buccal cell CK14 expression levels. CK14 was negatively correlated with plasma Mg²⁺ and LDL, while positively correlated with vitamin B12, red cell hematocrit/volume, and basophils in the MCI group and positively correlated with insulin and vitamin B12 in the AD group. The combined biomarker panel (CK14 expression, plasma vitamin B12, and homocysteine) was significantly lower in the MCI (p = 0.003) and AD (p = 0.0001) groups compared with controls. Receiver-operating characteristic curves yielded area under the curve (AUC) values of 0.829 for the MCI (p = 0.002) group and 0.856 for the AD (p = 0.0003) group. These complex associations of multiple related parameters highlight the differences between the MCI and AD cohorts and possibly an underlying metabolic pathology associated with the development of early memory impairment. The changes in buccal cell CK14 expression observed in this pilot study supports previous results suggesting the peripheral biomarkers and metabolic changes are not restricted to brain pathology alone in MCI and AD and could prove useful as a potential biomarker in identifying individuals with an increased risk of developing MCI and eventually AD.
authors.affiliation: CSIRO Food and Nutrition Flagship, Genome Health and Healthy Ageing, Adelaide, South Australia, Australia.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Leifert
authors.affiliation: CSIRO Food and Nutrition Flagship, Genome Health and Healthy Ageing, Adelaide, South Australia, Australia.
authors.forename: Tori
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.|Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia.
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rainey-Smith
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: National Ageing Research Institute, Parkville, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: CSIRO Food and Nutrition Flagship, Genome Health and Healthy Ageing, Adelaide, South Australia, Australia.
authors.forename: S Lance
authors.initials: SL
authors.lastname: Macaulay
authors.affiliation: CSIRO Food and Nutrition Flagship, Genome Health and Healthy Ageing, Adelaide, South Australia, Australia.
authors.forename: Maxime
authors.initials: M
authors.lastname: François
authors.affiliation: CSIRO Food and Nutrition Flagship, Genome Health and Healthy Ageing, Adelaide, South Australia, Australia.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Fenech
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology; D057205:Automation, Laboratory / Q000379:methods; D015415:Biomarkers / Q000097:blood; D002413:Cations, Divalent / Q000097:blood; D002610:Cheek; D008078:Cholesterol, LDL / Q000097:blood; D060825:Cognitive Dysfunction / Q000097:blood* / Q000473:pathology; D015331:Cohort Studies; D004909:Erythrocyte Indices; D005260:Female; D006711:Homocystine / Q000097:blood; D006801:Humans; D053547:Keratin-14 / Q000378:metabolism*; D008274:Magnesium / Q000097:blood; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D010865:Pilot Projects; D012306:Risk; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D015415:Biomarkers; D002413:Cations, Divalent; D008078:Cholesterol, LDL; D053547:Keratin-14; D006711:Homocystine; D008274:Magnesium; D014805:Vitamin B 12
keywords: Alzheimer’s disease; buccal mucosa; cytokeratin; imaging; immunofluorescence; mild cognitive impairment