Asthma aggravates alzheimer's disease by up-regulating NF- κB signaling pathway through LTD4.

Clinical studies have shown that asthma is a risk factor for dementia or Alzheimer's disease (AD). To investigate whether asthma aggravates AD in APP/PS1 mice and explore the potential mechanisms, an asthma model was established using six-month-old APP/PS1 mice, and montelukast was used as a therapeutic agent in APP/PS1 mice with asthma. The Morris water maze test showed that asthma aggravates spatial learning and memory abilities. Asthma also upregulates the NF-κB inflammatory pathway in APP/PS1 mice and promotes the expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), amyloid-ß (Aß) deposition, neuronal damage, synaptic plasticity deficiency, activation of microglia and astrocytes. The level of LTD4 and its receptor CysLT1R in the hippocampus of APP/PS1 mice after the asthma modeling was established was higher than that in APP/PS1 mice, suggesting that asthma may affect the pathology of AD through LTD4 and its receptor Cys-LT1R. Montelukast ameliorates these pathological changes and cognitive impairment. These results suggest that asthma aggravates AD pathology and cognitive impairment of APP/PS1 mice via upregulation of the NF-κB inflammatory pathway, and montelukast ameliorates these pathological changes.

The Association Between Cognition of Obstructive Sleep Apnea Patients and Urinary AD7c-NTP Level: Investigation and Application.

BACKGROUND: Obstructive sleep apnea (OSA) is a multi-component disorder, which has many comorbidities, including cognitive impairment. Although its potential risk factors were unknown, they could affect the patient's quality of life and long-term prognosis. OBJECTIVE: The purpose of this study was to investigate the application of urinary Alzheimer's disease-associated neurofilament protein (AD7c-NTP) levels in the assessment of cognitive impairment in OSA patients, and to analyze the predictive value of potential high-risk factors on cognitive impairment in OSA patients. METHODS: 138 young and middle-aged adults were recruited and underwent overnight polysomnographic recording, Montreal Cognitive Assessment (MoCA), and urinary AD7c-NTP test. AD7c-NTP and other factors were further applied as biomarkers to develop a cognition risk prediction model. RESULTS: Compared with the control, OSA patients showed significantly lower MoCA scores and higher urinary AD7c-NTP concentrations, while the severe OSA group appeared more significant. The urinary AD7c-NTP level of the OSA cognitive impairment group was higher than that of the non-cognitive impairment group. The results of regression analysis showed that urinary AD7c-NTP level was an independent predictor of cognitive impairment in OSA patients. Based on urinary AD7c-NTP levels and other selected factors, a multimodal prediction model for assessing the risk of cognitive impairment in OSA patients was initially established. CONCLUSION: The increased urinary AD7c-NTP level could be used as a relevant peripheral biomarker of cognitive impairment in OSA patients. A model using urinary AD7c-NTP combined with other factors was developed and could accurately assess the cognition risk of OSA patients.

The relationship between urinary Alzheimer-associated neuronal thread protein and blood biochemical indicators in the general population.

Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) is elevated in early Alzheimer's disease (AD) and mild cognitive impairment, and is considered a biomarker for the early diagnosis of AD. However, it has not yet been investigated whether urinary AD7c-NTP is elevated with increases in blood biochemical indicators related to AD risk factors. We recruited 2180 participants, aged 35-93 years, from communities of four districts in Beijing. Blood biochemical indicators, including blood glucose, blood lipids, renal function, and high-sensitivity C-reactive protein, were measured using routine methods. Urinary AD7c-NTP was detected using an enzyme-linked immunosorbent assay AD7c-NTP kit. In the general population, there were no significant differences in urinary AD7c-NTP levels in subjects with different Mini-Mental State Examination levels or C-reactive protein values. After adjusting for age and sex, there were significant differences in urinary AD7c-NTP levels between different education levels, marital statuses, blood glucose, blood lipids, and kidney function. There was a negative correlation between urinary AD7c-NTP levels and serum creatinine (r = -0.128). There was a positive correlation between urinary AD7c-NTP levels and HbA1c (r = 0.104), insulin (r = 0.101), and triglycerides (r = 0.093). Urinary AD7c-NTP might be useful as a potential indicator to predict AD risk.

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

We investigated the relationship between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) levels and apolipoprotein epsilon 4 (ApoE ɛ4) alleles, as well as other factors that cause cognitive decline, in the cognitively normal population. We recruited 329 cognitively normal right-handed Han Chinese subjects who completed ApoE gene testing and urinary AD7c-NTP testing. There was no significant difference in urinary AD7c-NTP levels between the normal control and subjective cognitive decline groups. Urinary AD7c-NTP levels were significantly higher in subjects with ApoE ɛ3/4 and 4/4 [0.6074 (0.6541) ng/mL] than in subjects without ApoE ɛ4 [0.4368 (0.3392) ng/mL and 0.5287 (0.3656) ng/mL], and urinary AD7c-NTP levels positively correlated with ApoE genotype grade (r = 0.165, p = 0.003). There were significant differences in urinary AD7c-NTP levels between subjects with and without a history of coronary heart disease or diabetes. Urinary AD7c-NTP levels were not related to years of education, nature of work, family history of dementia, a history of hypertension, stroke, anemia, or thyroid dysfunction. Urinary AD7c-NTP levels were positively correlated with ApoE grade in the cognitively normal population. The relationship between risk factors of cognitive decline and urinary AD7c-NTP levels provides a new way for us to understand AD and urinary AD7c-NTP.

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

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.