Blood biomarker related to anxiety and depression of Parkinson's disease and application of blood biomarker

Abstract

The invention discloses a blood biomarker related to anxiety and depression of Parkinson's disease and application of the blood biomarker, and belongs to the technical field of biomedicine. A large sample of peripheral blood of a Parkinson's disease patient is collected, the levels of baseline plasma neurofilament light-chain protein, colloidal fibrillary acidic protein and p-tau181 of all participants are detected by using a hypersensitive single-molecule array (simoa) technology, and depression and anxiety symptoms of the patient are evaluated by using a Hamilton depression scale and a Hamilton anxiety scale. Follow-up visit is conducted on the patient once a year, follow-up visit is continuously conducted for 5 years, and during follow-up visit, the HAMD scale and the HAMA scale are used again for evaluating depression and anxiety of the patient and measuring the plasma biomarker level of the patient. Statistical analysis is carried out by using a generalized estimation equation and a linear mixed model, and the result shows that the blood plasma GFAP level can predict anxiety and depression of the Parkinson's disease patient.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and in particular relates to a blood biomarker associated with Parkinson's disease anxiety and depression and an application thereof. Background Art

[0002] Parkinson's disease is one of the most common neurodegenerative diseases. Its main clinical manifestations include motor symptoms such as bradykinesia, resting tremor, and rigidity, as well as non-motor symptoms such as constipation, hyposmia, anxiety and depression, cognitive decline, and sleep disorders. Among them, anxiety and depression are common non-motor symptoms in patients with Parkinson's disease, which can seriously affect the quality of life of patients and increase the risk of suicide. PET imaging of serotonin-ergic presynaptic transporters has been found to be a marker for depression in patients with Parkinson's disease, but PET imaging is expensive and radioactive. Therefore, it is urgent to find blood biomarkers that can replace PET imaging to predict anxiety and depression in patients with Parkinson's disease. Summary of the invention

[0003] The present invention provides use of a reagent for detecting NfL and GFAP levels in plasma in preparing a product for judging the degree of depression in Parkinson's disease patients.

[0004] Furthermore, the product is a kit.

[0005] The present invention also provides the use of a reagent for detecting the level of NfL in plasma in the preparation of a product for judging the anxiety level of Parkinson's disease patients.

[0006] Furthermore, the product is a kit.

[0007] The present invention also provides a product for judging the depression degree of Parkinson's patients, wherein the product contains reagents for detecting the levels of NfL and GFAP in human plasma.

[0008] The present invention also provides a product for judging the anxiety level of Parkinson's patients, wherein the product contains a reagent for detecting the level of NfL in human plasma.

[0009] Furthermore, the product is a kit.

[0010] Compared with the prior art, the present invention has the following beneficial effects:

[0011] The present invention provides a new technical means for predicting anxiety and depression in Parkinson's disease patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 These are the correlation data between depression and plasma NfL and GFAP levels in Example 1, as well as the correlation data between anxiety and plasma NfL levels.

[0013] Figure 2 These are the data showing significant correlations between HAMD score and plasma NfL and GFAP, and the data showing significant correlations between HAMA score and plasma NfL in Example 1.

[0014] Figure 3 This is a graph showing the relationship between the baseline GFAP level and the HAMA score and the HAMD score in Example 1. DETAILED DESCRIPTION

[0015] Example 1

[0016] The inventors collected peripheral blood from a large sample of Parkinson's disease patients, and used ultrasensitive single molecule array (simoa) technology to detect the baseline plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and p-tau181 levels of all participants. The Hamilton depression rating scale (HAMD, 24-item version) and Hamilton anxiety rating scale (HAMA) were used to assess the depression and anxiety symptoms of patients. The patients were followed up once a year for 5 consecutive years. During the follow-up, the HAMD and HAMA scales were used again to assess the depression and anxiety of the patients and measure the plasma biomarker levels of the patients. Statistical analysis was performed using generalized estimating equations and linear mixed models, and the results showed that plasma GFAP levels can predict the occurrence of anxiety and depression in patients with Parkinson's disease.

[0017] The specific process is as follows:

[0018] 1) 184 patients with Parkinson's disease were included in the baseline, and their demographic characteristics such as gender, age, height, weight, and clinical characteristics such as disease course and medication were collected. UPDRS-III was used to evaluate the patient's motor symptoms. The Parkinson's disease sleep scale 2nd version (PDSS-2) was used to evaluate the patient's sleep quality. The Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to evaluate the patient's depression and anxiety symptoms. The Montreal cognitive assessment (MoCA) was used to evaluate the patient's cognitive function. The plasma NfL, GFAP, and p-tau181 levels of the patients were detected using simoa technology.

[0019] 2) Annual follow-up will be conducted on the included Parkinson's disease patients, once a year for a total of 5 years. During the follow-up, the patients' HAMD and HAMA scores will be re-evaluated to determine whether the patients have depression and anxiety, and the patients' motor symptoms, cognitive function, and plasma NfL, GFAP, and p-tau181 levels will be re-evaluated.

[0020] 3) Generalized estimating equations and linear mixed models were used to analyze the correlation between hematological indicators and depression and anxiety.

[0021] The association of plasma biomarkers with clinical characteristics and the presence of depression or anxiety during the 2-year follow-up was investigated using a generalized estimating equation (GEE) model that allowed for associations in repeated measures in the same patient. In this model, the presence of depression or anxiety was set as the dependent variable, and repeated measures of each biomarker were treated as independent repeated variables. Analyses were performed for each biomarker separately controlling for sex, age, disease duration, and follow-up time.

[0022] Linear mixed-effects models were used to investigate the associations between plasma biomarkers and clinical characteristics and severity of depression or anxiety (measured by HAMD or HAMA scores) during the 2-year follow-up period, accounting for repeated measures and variable follow-up time. Each model used the time-varying HAMD or HAMA score as the dependent variable, with repeated measures of each biomarker considered as a fixed effect and the intercept as a random effect. Analyses were performed separately for each biomarker, controlling for sex, age, disease duration, and follow-up time.

[0023] The adjusted GEE model showed that depression was associated with plasma NfL (OR 1.068 [1.016-1.123], p = 0.010) and GFAP levels (OR 1.016 [1.005-1.028], p = 0.005), and anxiety was associated with plasma NfL levels (OR 1.060 [1.017-1.106], p = 0.006). Figure 1 The adjusted linear mixed effects model showed that the HAMD score was significantly correlated with plasma NfL (β0.113 [0.015-0.211], p = 0.024) and GFAP (β0.021 [0.0005-0.042], p = 0.045), and the HAMA score was significantly correlated with plasma NfL (β0.163 [0.071-0.255], p = 0.001) ( Figure 2 ).

[0024] Example 2

[0025] Linear mixed-effects models were used to explore whether baseline plasma biomarker levels could predict long-term depression and anxiety progression in PD patients. The predictive ability of baseline plasma biomarkers on progression was tested by the interaction between baseline plasma biomarkers and follow-up time. Baseline plasma biomarkers were transformed into binary variables using the median in the analysis. Baseline plasma biomarkers, follow-up time, and their interactions were considered fixed effects, while the intercept was considered a random effect. Time-varying scores of HAMA and HAMD were used as dependent variables; sex, age, and disease duration were used as covariates.

[0026] The higher the baseline GFAP level, the slower the decline of HAMA score (β0.572 [0.029-1.115], p = 0.039), and the slower the decline of HAMD score (β0.488 [-0.176-1.152], p = 0.15) ( Figure 3 ), that is, plasma NfL and GFAP levels can be used as hematological biomarkers of depression and anxiety in patients with Parkinson's disease.

[0027] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. Use of reagents for detecting NfL and GFAP levels in human plasma in the preparation of products for determining the degree of depression in Parkinson's patients.

2. The use according to claim 1, characterized in that The product is a test kit.

3. Use of a reagent for detecting NfL levels in human plasma in the preparation of a product for determining the anxiety level of Parkinson's disease patients.

4. The use according to claim 3, characterized in that The product is a test kit.

5. A product for judging the degree of depression in Parkinson's patients, characterized in that: The product contains reagents for detecting the levels of NfL and GFAP in human plasma.

6. A product for judging the anxiety level of Parkinson's patients, characterized in that: The product contains a reagent for detecting the level of NfL in human plasma.

7. The product according to claim 5 or 6, characterized in that The product is a test kit.

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