Altered cytological parameters in buccal cells from individuals with mild cognitive impairment and Alzheimer's disease

Previous studies have shown that mild cognitive impairment (MCI) may be reflective of the early stages of more pronounced neurodegenerative disorders such as Alzheimer's disease (AD). There is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritized for primary preventative measures. The hypothesis was that a minimally invasive approach using cytological markers in isolated buccal mucosa cells can be used to identify individuals of both MCI and AD. An automated buccal cell assay was developed using laser scanning cytometry (LSC) to measure buccal cell type ratios, nuclear DNA content and shape, and neutral lipid content of buccal cells from clinically diagnosed AD (n=13) and MCI (n=13) patients prior to treatment compared to age- and gender-matched controls (n=26). DNA content was significantly higher in all cell types in both MCI (P<0.01) and AD (P<0.05) compared with controls mainly due to an increase in >2N nuclei. Abnormal nuclear shape (circularity) was significantly increased in transitional cells in MCI (P<0.001) and AD (P<0.01) when compared to controls. In contrast, neutral lipid content (as measured by Oil red O "ORO" staining) of buccal cells was significantly lower in the MCI group (P<0.05) compared with the control group. The ratio of DNA content/ORO in buccal basal cells for both MCI and AD was significantly higher compared to the control group, with ratios for MCI being approximately 2.8-fold greater (P<0.01) and AD approximately 2.3-fold greater (P<0.05) than the control group. Furthermore, there was a strong negative correlation between buccal cell DNA content and ORO content in the AD group (r²=0.75, P<0.0001) but not in MCI or controls. The changes in the buccal cell cytome observed in this study could prove useful as potential biomarkers in identifying individuals with an increased risk of developing MCI and eventually AD.