Early diagnosis of Alzheimer's disease from elevated olfactory mucosal miR-206 level.

MicroRNA-206, which suppresses the expression of brain-derived neurotrophic factor, is known to be elevated in the brains of Alzheimer's disease (AD) patients. We performed intranasal biopsy of the olfactory epithelia of early dementia patients (n = 24) and cognitively healthy controls (n = 9). Patients with significant depression (n = 8) were analyzed separately, as their cognitive impairments were thought to be caused by their depression. Real-time PCR was performed on the biopsied tissues. The relative microRNA-206 level exhibited a 7.8-fold increase (P = 0.004) in the mild cognitive impairment group (CDR 0.5; n = 13) and a 41.5-fold increase (P < 0.001) in the CDR 1 group (n = 11). However, this level was not increased in the depression group, even in those with cognitive decline. Using the optimal cutoff value, the sensitivity/specificity for diagnosing CDR 0.5 and CDR 1 dementia were 87.5%/94.1% and 90.9%/93.3%, respectively. In ROC analysis, the AUCs were 0.942 and 0.976 in the CDR 0.5 and CDR 1 groups, respectively. The olfactory mucosal microRNA-206 level and cognitive assessment scores were significantly correlated in the non-depressed subjects with cognitive impairment. In conclusion, the olfactory mucosal microRNA-206 level can be easily measured, and it can be utilized as an excellent biomarker for the diagnosis of early AD, including mild cognitive impairment.