Buccal Cell Cytokeratin 14 Correlates with Multiple Blood Biomarkers of Alzheimer’s Disease Risk

Article type: Research Article

Authors: Leifert, Wayne R.^{a; *} | Nguyen, Tori^a | Rembach, Alan^{b; 1} | Martins, Ralph^{c; d} | Rainey-Smith, Stephanie^c | Masters, Colin L.^b | Ames, David^e | Rowe, Christopher C.^f | Macaulay, S. Lance^a | François, Maxime^a | Fenech, Michael F.^a | and the Australian Imaging, Biomarkers and Lifestyle Study Research Group^g

Affiliations: [a] CSIRO Food and Nutrition Flagship, Genome Health and Healthy Ageing, Adelaide, South Australia, Australia | [b] The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia | [c] Centre of Excellence for Alzheimer’s Disease Research & Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia | [d] Sir James McCusker Alzheimer’s Disease Research Unit (Hollywood Private Hospital), Perth, Western Australia | [e] National Ageing Research Institute, Parkville, Victoria, Australia | [f] Department of Nuclear Medicine & Centre for PET, Austin Health, Heidelberg, Victoria, Australia | [g] http://aibl.csiro.au/about/aibl-research-team/

Correspondence: [*] Correspondence to: Dr. Wayne Leifert, CSIRO Food andNutrition Flagship, Genome Health and Healthy Ageing, Gate 13, Kintore Avenue, Adelaide, South Australia, 5000, Australia. Tel.: +91 08 8303 8821l; [email protected]

Note: [1] Deceased.

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.

Keywords: Alzheimer’s disease, buccal mucosa, cytokeratin, imaging, immunofluorescence, mild cognitive impairment

DOI: 10.3233/JAD-150330

Journal: Journal of Alzheimer's Disease, vol. 48, no. 2, pp. 443-452, 2015