Urinary Alzheimer-Associated Neuronal Thread Protein is not Elevated in Patients with Subjective Cognitive Decline and Patients with Depressive State

Abstract

Subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease (AD). Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) has been identified as a biomarker for AD. It was hypothesized that if urinary AD7c-NTP were also elevated in SCD, as it is in prodromal AD (mild cognitive impairment stage), it could be a convenient and efficient clinical biomarker for the early diagnosis of SCD. SCD is often accompanied by a depressive state (DS), and the impact of DS on urinary AD7c-NTP levels remains unknown. A total of 297 right-handed Chinese Han subjects were recruited, including 98 subjects with SCD, 92 patients with DS, and 107 well-matched cognitively normal controls (NC). The levels of AD7c-NTP in urine samples were measured using an enzyme-linked immunosorbent assay AD7c-NTP kit. Our results demonstrated that urinary AD7c-NTP levels in the SCD group (0.7561 ± 0.5657 ng/mL) were not significantly higher than in either the DS (0.7527 ± 0.5607 ng/mL) or NC (0.7214 ± 0.5077 ng/mL) groups. Furthermore, urinary AD7c-NTP levels were not correlated with Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores, but they were negatively associated with Mini-Mental State Examination scores (r = -0.222, p = 0.033) and Montreal Cognitive Assessment-Basic scores (r = -0.207, p = 0.048). Urinary AD7c-NTP level is not elevated in SCD and is unaffected by DS. Urinary AD7c-NTP may therefore not be a good potential biomarker for SCD and DS, although it may become elevated with more severe cognitive decline.

Relationship between Urinary Alzheimer-Associated Neuronal Thread Protein and Apolipoprotein Epsilon 4 Allele in the Cognitively Normal Population

“…In the present study, it was revealed that the levels of urinary AD7c-NTP were not higher in SCD patients compared with the NC group. This result is consistent with previous results from our research group [15]. The reason for these results may be that SCD is still a very early stage of the disease when neuropsychological test scores are normal; thus, tau protein may not be increased or detected at this stage [41].…”

“…In addition, a previous study reported that urinary AD7c-NTP is elevated in late-life depression with cognitive impairment [13]. Furthermore, existing research recognizes that urinary AD7c-NTP has a critical role in cognitive decline, but not in depression or other diseases [12][13][14][15]. Urinary AD7c-NTP testing is noninvasive, radiation-free, repeatable, and easy to carry out.…”

“…Therefore, urinary AD7c-NTP may be a promising peripheral biomarker for detecting cognitive decline and disease progression [16]. Although previous studies have reported that cognitive decline is associated with elevated urinary AD7c-NTP, it is not clear which factors, aside from decreased cognitive function, are associated with elevated urinary AD7c-NTP [13,15,17,18]. It has not been reported whether other medical history factors that may lead to a decline in cognitive function, such as carbon monoxide poisoning (COP), general anesthesia, or thyroid dysfunction, are associated with urinary AD7c-NTP levels in the normal cognitive population.…”

Correlation Between Urine Formaldehyde and Cognitive Abilities in the Clinical Spectrum of Alzheimer’s Disease

“…Urine AD7c-NTP was increased in MCI and AD (Youn et al, 2011;Ma et al, 2015). However, AD7c-NTP was not elevated in patients with SCD (Li et al, 2019). While there have been considerable advancements in the field, the lack of changes on the above-mentioned markers in the preclinical stage of AD poses significant challenges for the use of such biomarkers in the clinical practice.…”

The fluid biomarkers of Alzheimer’s disease

“…In a pilot study, a targeted and quantitative metabolomics approach is applied, and several panels composed of urinary metabolites are identified to distinguish MCI and AD from cognitively healthy controls with high sensitivity and specificity [102]. Several novel urinary biomarkers for the early diagnosis of AD have been discovered, and some of them are Alzheimer-associated neuronal thread protein (AD7c-NTP) [103][104][105][106], monocyte chemoattractant protein-1 (MCP-1) [107], and dysregulated arginine metabolism [108].…”