High content, multi-parameter analyses in buccal cells to identify Alzheimer's disease

Maxime François, Michael F. Fenech, Philip Thomas, Maryam Hor, Alan Rembach, Ralph N. Martins, Stephanie R. Rainey-Smith, Colin L. Masters, David Ames, Christopher C. Rowe, S. Lance Macaulay, Andrew F. Hill, Wayne R. Leifert*, The AIBL Research Group

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Alzheimer’s disease (AD) is a degenerative brain disorder and is the most common form of dementia. Minimally invasive approaches are required that combine biomarkers to identify individuals who are at risk of developing mild cognitive impairment (MCI) and AD, to appropriately target clinical trials for therapeutic discovery as well as lifestyle strategies aimed at prevention. Buccal mucosa cells from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing cohort (n=60) were investigated for cytological markers that could be used to identify both MCI and AD individuals. Visual scoring of the buccal cytome demonstrated a significantly lower frequency of basal and karyorrhectic cells in the MCI group compared with controls. A high content, automated assay was developed using laser scanning cytometry to simultaneously measure cell types, nuclear DNA content and aneuploidy, neutral lipid content, putative Tau and amyloid-β (Aβ) in buccal cells. DNA content, aneuploidy, neutral lipids and Tau were similar in all groups. However, there was significantly lower Tau protein in both basal and karyolytic buccal cell types compared with differentiated buccal cells. Aβ, as measured by frequency of cells containing Aβ signal, as well as area and integral of Aβ signal, was significantly higher in the AD group compared with the control group. Buccal cell Aβ was correlated with mini-mental state examination (MMSE) scores (r = -0.436, P=0.001) and several blood-based biomarkers. Combining newly identified biomarkers from buccal cells with those already established may offer a potential route for more specific biomarker panels which may substantially increase the likelihood of better predictive markers for earlier diagnosis of AD.

Original languageEnglish
Pages (from-to)787-799
Number of pages13
JournalCurrent Alzheimer Research
Volume13
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

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Keywords

  • Alzheimer's disease
  • Amyloid
  • Buccal cells
  • DNA content
  • Laser scanning cytometry
  • Mild cognitive impairment
  • Neutral lipids

Cite this

François, M., Fenech, M. F., Thomas, P., Hor, M., Rembach, A., Martins, R. N., ... The AIBL Research Group (2016). High content, multi-parameter analyses in buccal cells to identify Alzheimer's disease. Current Alzheimer Research, 13(7), 787-799. https://doi.org/10.2174/1567205013666160315112151