The association between urinary Alzheimer-associated neuronal thread protein and cognitive impairment in late-life depression: A controlled pilot study

Accumulation of tau protein is associated with both Alzheimer’s disease (AD) and late-life depression (LLD). Alzheimer-associated neuronal thread protein (AD7c-NTP), which is closely linked with the tau protein, is elevated in the cerebrospinal fluid and urine of AD patients. This study examined the association between urinary AD7c-NTP and late-life depression with cognitive impairment. One hundred and thirty-eight subjects were recruited into late-life depression with cognitive impairment (LLD-CI, n=52), late-life depression without cognitive impairment (LLD-NCI, n=29), AD (n=27), and healthy control (HC, n=30) groups. The level of urinary AD7c-NTP was measured using the enzyme-linked immunosorbent assay method. The Montreal Cognitive Assessment scale (MoCA), Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Rating Scale (HAMA) were used to assess cognitive functions and depressive and anxiety symptoms in the AD and LLD groups. Urinary levels of AD7c-NTP in the LLD-CI group (1.0±0.7ng/ml) were significantly higher than both the LLD-NCI (0.5±0.3ng/ml) and HC groups (0.5±0.3ng/ml), but lower than in the AD group (1.6±1.7 ng/ml). No significant associations were found in the level of urinary AD7c-NTP in relation to age, gender, education and MoCA in the LLD-CI group. The level of urinary AD7c-NTP appears to be associated with cognitive impairment in late-life depression and may be a potential biomarker for early identification of cognitive impairment in LLD

MicroRNA-29c-3p in dual-labeled exosome is a potential diagnostic marker of subjective cognitive decline

Objective: The present study aimed to determine whether peripheral blood neural cell adhesion molecule (NCAM)/amphiphysin 1 dual-labeled exosomal proteins and microRNAs (miRs) might serve as a marker for the early diagnosis of Alzheimer's disease (AD). Methods: This observational, retrospective, multicenter study used a two-stage design conducted in Beijing and Shanghai, China. The subjects included 76 patients with subjective cognitive decline (SCD), 80 with amnestic mild cognitive impairment (aMCI), 76 with dementia of Alzheimer's type (AD), 40 with vascular dementia (VaD), and 40 controls in the discovery stage. These results were confirmed in the verification stage. The levels of Aβ42, Aβ42/40, T-Tau, P-T181-tau, neurofilament light chain (NfL), and miR-29c-3p in peripheral blood amphiphysin 1 single-labeled and NCAM/amphiphysin 1 dual-labeled exosomes were captured and detected by immunoassay. Results: In the discovery stage, the levels of Aβ42 and miR-29c-3p in peripheral blood NCAM/amphiphysin 1 dual-labeled exosome of the SCD group were significantly higher than those in control and VaD groups (all P < 0.05). The verification stage further confirmed the results of the discovery stage. Plasma NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p showed a good diagnostic performance. The NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p had the highest AUC for diagnosis of SCD. The levels of Aβ42, Aβ42/40, Tau, P-T181-tau, and miR-29c-3p in peripheral blood exosomes were correlated to those in CSF (all P < 0.05). The combination of exosomal biomarkers had slightly higher diagnostic efficiency than the individual biomarkers and that the exosomal biomarkers had the same diagnostic power as the CSF biomarkers. Conclusion: The plasma NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p had potential advantages in the diagnosis of SCD