Application of aldosterone in diagnosis of amyotrophic lateral sclerosis

Abstract

The invention provides application of aldosterone in diagnosis of amyotrophic lateral sclerosis, and particularly provides application of a reagent for detecting the aldosterone level in a sample in preparation of products for in-vitro diagnosis, auxiliary diagnosis and / or illness monitoring of amyotrophic lateral sclerosis. By simply detecting the aldosterone level in a serum sample, accurate diagnosis and illness monitoring of ALS can be realized.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and in particular to application of aldosterone in diagnosing amyotrophic lateral sclerosis. Background Art

[0002] Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons in the brain and spinal cord. Patients often experience initial localized muscle weakness and atrophy, which then spreads throughout the body, ultimately leading to life-threatening respiratory failure. Its pathogenesis remains unclear, and clinical treatment options are limited, primarily symptomatic and supportive, with suboptimal results and limited potential for a cure. Currently, the diagnosis of ALS relies primarily on observation of clinical symptoms and signs, neuroelectrophysiological testing, and imaging studies. However, early diagnosis is difficult to achieve using clinical and neuroelectrophysiological testing alone. Existing ALS diagnostic and treatment methods lack accuracy, disease monitoring, and personalized treatment, failing to meet clinical needs. Furthermore, ALS is a progressive disease. Further development of ALS-related biomarkers for monitoring disease progression and predicting patient prognosis would be of great benefit to the clinical diagnosis and treatment of ALS.

[0003] Based on the above background, providing reliable biomarkers related to ALS and their application in diagnosing ALS are of great significance to the field of ALS treatment. Summary of the Invention

[0004] To address the above issues, the present invention provides a biomarker that can be used for disease diagnosis, condition monitoring, treatment plan selection and prognosis assessment in patients with amyotrophic lateral sclerosis.

[0005] To achieve the above objectives, the specific technical solutions provided by the present invention are as follows:

[0006] A first aspect of the present invention provides use of a reagent for detecting aldosterone levels in a sample in the preparation of a product for in vitro diagnosis, auxiliary diagnosis and / or disease monitoring of amyotrophic lateral sclerosis.

[0007] Aldosterone is a steroid hormone (mineralocorticoid family) that enhances the reabsorption of ions and water molecules by the kidneys. Its chemical formula is C 21 H 28 O5 mainly acts on the kidneys and is a hormone that enhances the kidney's reabsorption of ions and water.

[0008] Furthermore, the reagent for detecting the aldosterone level in the sample detects the aldosterone level in the sample by one or more of the following methods: radioimmunoassay, chemiluminescence, enzyme-linked immunosorbent assay, chromatography, spectroscopy, mass spectrometry, and chromatography-mass spectrometry.

[0009] Furthermore, the product includes a test kit and a chip.

[0010] As used herein, the term "sample" refers to a composition obtained or derived from a subject (e.g., an individual of interest), comprising cellular entities and / or other molecular entities characterized and / or identified based on physical, biochemical, chemical, and / or physiological characteristics. The sample to be tested can be derived from the subject's blood, other fluid samples of biological origin, and tissue samples, such as biopsy tissue samples, or tissue cultures or cells derived therefrom. Tissue samples can be derived from solid tissues, such as fresh, frozen, and / or preserved organ or tissue samples, biopsies, or aspirates; blood or any blood component; body fluids; cells from any time during an individual's gestation or development; or plasma. Samples include biological samples that have been manipulated in any manner after their acquisition, such as by reagent treatment, stabilization, enrichment for specific components (e.g., proteins or polynucleotides), or embedding in a semisolid or solid matrix for sectioning. The cells can be animal cells, such as those derived from humans, chimpanzees, monkeys, horses, cows, sheep, pigs, donkeys, camels, dogs, rabbits, cats, rats, mice, fish, birds, or insects, as are well known in the art. The subject includes mammals, preferably primates, and particularly preferably humans.

[0011] Furthermore, the sample includes serum, plasma, urine, blood, tissue or cell culture fluid.

[0012] A second aspect of the present invention provides a product for diagnosing, assisting in the diagnosis of amyotrophic lateral sclerosis and / or monitoring the condition of amyotrophic lateral sclerosis patients, wherein the product comprises a reagent for detecting the aldosterone level in a sample.

[0013] Furthermore, the product includes a test kit and a chip.

[0014] Furthermore, the reagent for detecting the aldosterone level in the sample detects the aldosterone level in the sample by one or more of the following methods: radioimmunoassay, chemiluminescence, enzyme-linked immunosorbent assay, chromatography, spectroscopy, mass spectrometry, and chromatography-mass spectrometry.

[0015] Furthermore, the sample includes serum, plasma, urine, blood, tissue or cell culture fluid.

[0016] Furthermore, the product also includes reagents for processing samples.

[0017] The third aspect of the present invention provides the use of an aldosterone receptor antagonist in the preparation of a drug for treating amyotrophic lateral sclerosis. The aldosterone receptor antagonist includes spironolactone, eplerenone, and finerenone.

[0018] Aldosterone exerts its effects through aldosterone receptors, which are widely distributed in various tissue cells. In the kidneys, aldosterone receptors are found in podocytes, macrophages, mesangial cells, and fibroblasts, and in the cardiovascular system, in cardiomyocytes, macrophages, fibroblasts, endothelial cells, and vascular smooth muscle cells. Aldosterone receptor antagonists include steroidal aldosterone receptor antagonists (spironolactone and eplerenone), and nonsteroidal aldosterone receptor antagonists (finerenone).

[0019] Furthermore, the aldosterone receptor antagonist is spironolactone.

[0020] A fourth aspect of the present invention provides the use of aldosterone as a target in screening drugs for preventing or treating amyotrophic lateral sclerosis, wherein the screening comprises determining whether the drug is a candidate drug for preventing or treating amyotrophic lateral sclerosis based on its effects on aldosterone before and after use.

[0021] Furthermore, if the aldosterone level decreases after the use of the drug compared to before use, the drug is a candidate drug for preventing or treating amyotrophic lateral sclerosis; if the aldosterone level increases or remains unchanged after the use of the drug compared to before use, the drug is not a candidate drug for preventing or treating amyotrophic lateral sclerosis.

[0022] A fifth aspect of the present invention provides a computer-implemented method for constructing an amyotrophic lateral sclerosis diagnostic model, the method comprising the steps of obtaining aldosterone expression level data of amyotrophic lateral sclerosis patients and healthy controls, and constructing a diagnostic model based on the expression level data.

[0023] In some embodiments of the present invention, methods for constructing a predictive model are known to those skilled in the art, and the steps of correlating aldosterone levels with a probability or risk can be implemented and achieved in various ways. Preferably, the measured concentrations of the marker and one or more other markers are mathematically combined, and the combined value is correlated to the underlying diagnostic question. The measured aldosterone values ​​can be combined by any suitable prior art mathematical method and the predictive model constructed algorithmically.

[0024] In the context of the present invention, the term "algorithm" refers to the use of a computer to simulate or implement human learning activities. Technicians typically use different development tools to build machine learning algorithm models. The development tools include but are not limited to TensorFlow, Scikit Learn, PyTorch, OpenNN, RapidMiner, Azure Machine Learning, Apache Mahout, Shogun, KNIME, Vertex AI, H2Oai, Anaconda, Keras, Tableau, Fast.ai, Catalyst, Amazon ML, MLJAR, Spell. The algorithm models include but are not limited to linear regression models, logistic regression models, Lasso regression models, Ridge regression models, linear discriminant analysis models, nearest neighbor models, decision tree models, perceptron models, neural network models, support vector machine models, naive Bayes models, AdaBoost models, GBDT models, XGBoost models, LightGBM models, CatBoost models, or random forest models.

[0025] Furthermore, the diagnostic model predicts whether the subject has ALS, whether the subject is at risk of developing ALS, or monitors the progression of ALS in a subject based on the aldosterone level data in the sample.

[0026] Furthermore, the construction of the diagnostic model based on the expression level data is performed by an algorithm.

[0027] Furthermore, the algorithm includes one or more of a linear regression model, a logistic regression model, a Lasso regression model, a Ridge regression model, a linear discriminant analysis model, a nearest neighbor model, a decision tree model, a perceptron model, a neural network model, a support vector machine model, a naive Bayes model, an AdaBoost model, a GBDT model, an XGBoost model, a LightGBM model, a CatBoost model or a random forest model.

[0028] A sixth aspect of the present invention provides a computer-implemented system for diagnosing and / or monitoring amyotrophic lateral sclerosis, the system comprising:

[0029] Data acquisition unit: obtaining aldosterone level data in samples;

[0030] A data classification unit: inputting the aldosterone level data into a constructed diagnostic model, wherein the diagnostic model is constructed based on the method described in the fifth aspect of the present invention;

[0031] Output unit: outputs and stores analysis results, indicating whether the subject has amyotrophic lateral sclerosis, whether the subject has a risk of developing amyotrophic lateral sclerosis, or monitors the disease progression of a subject with amyotrophic lateral sclerosis.

[0032] A seventh aspect of the present invention provides a computer device for diagnosing and / or monitoring amyotrophic lateral sclerosis, the computer device comprising:

[0033] a processor adapted to implement the instructions; and

[0034] A memory adapted to store a plurality of instructions adapted to be loaded by a processor and executed by the processor:

[0035] Acquire data, obtain aldosterone level data in the sample;

[0036] Processing the data, inputting the aldosterone level data into a constructed diagnostic model, wherein the diagnostic model is constructed based on the method described in the fifth aspect of the present invention;

[0037] Outputting a result: Outputting and storing an analysis result, indicating whether the subject has amyotrophic lateral sclerosis, whether the subject is at risk of developing amyotrophic lateral sclerosis, or monitoring the progression of the disease in a subject with amyotrophic lateral sclerosis.

[0038] Another aspect of the present invention provides a computer-readable medium having a plurality of instructions stored therein, wherein the instructions are suitable for being loaded by a processor and executing the following steps:

[0039] Acquire data, obtain aldosterone level data in the sample;

[0040] Processing the data, inputting the aldosterone level data into a constructed diagnostic model, wherein the diagnostic model is constructed based on the method described in the fifth aspect of the present invention;

[0041] Outputting a result: Outputting and storing an analysis result, indicating whether the subject has amyotrophic lateral sclerosis, whether the subject is at risk of developing amyotrophic lateral sclerosis, or monitoring the progression of the disease in a subject with amyotrophic lateral sclerosis.

[0042] It should be understood that the systems, devices, and methods described herein can be implemented in other ways. For example, the device embodiments described above are merely illustrative. For example, the module division is merely a logical functional division, and actual implementations may employ other division methods, such as combining or integrating multiple modules or components into another system, or omitting or disabling certain features. Furthermore, the coupling or direct coupling or communication connection shown or discussed may be an indirect coupling or communication connection between devices or modules via some interface, which may be electrical, mechanical, or other forms.

[0043] The modules described as separate components may or may not be physically separate, and the components shown as modules may or may not be physical units, that is, they may be located in one place or distributed across multiple network elements. Some or all of these units may be selected to achieve the purpose of this embodiment according to actual needs.

[0044] In addition, the functional modules in various embodiments of the present invention may be integrated into a single processing module, or each module may exist physically separately, or two or more modules may be integrated into a single module. The aforementioned integrated modules may be implemented in the form of hardware or software functional modules.

[0045] Advantages and beneficial effects of the present invention: The present invention provides a reliable biomarker aldosterone associated with amyotrophic lateral sclerosis and its application in diagnosing ALS. By simply detecting the aldosterone level in a sample, accurate diagnosis and disease monitoring of ALS can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 SOD1 G93A The results show that there are significant differences in aldosterone content and adrenal morphology between mice and B6 mice, where A represents SOD1 before onset, onset, and end-stage. G93A Results of aldosterone content in mouse lumbar spinal cord tissue; B is SOD1 G93A Adrenal gland morphology of mice (left) and B6 mice (right); CH stands for SOD1 G93A Figure 2: Changes in adrenal gland structure and cell morphology in mice as the disease progresses. CD is B6 mouse (90 days old), EF is SOD1 G93A In the onset stage of mice (90 days old), GH is SOD1 G93A Terminal stage of mice (120 days old).

[0047] Figure 2These are the results of aldosterone receptor antagonists delaying the onset of ALS. The left figure shows the statistical results of the onset time, and the right figure shows a representative picture of the onset period of the spironolactone-treated group (brown mice on the left) and the aldosterone-treated group (white mice on the right) of mice from the same litter.

[0048] Figure 3 The figures show the levels of astrocytes and inflammatory factors in the lumbar spinal cord tissue of ALS mice in the aldosterone-treated group, spironolactone-treated group and corresponding control group. A is the result of immunofluorescence staining of astrocytes, and B is a representative image of the expression level of inflammatory factors detected by WB.

[0049] Figure 4 These are statistical graphs of the levels of astrocytes and inflammatory factors (GFAP, CD11b, IKB-α, Pp65, IL-1, TNF-α, and IL-3) in the lumbar cord tissue of ALS mice in the aldosterone-treated group, spironolactone-treated group, and corresponding control group. A is the statistical graph of GFAP levels in the aldosterone-treated group, spironolactone-treated group, and corresponding control group; B is the statistical graph of CD11b levels in the aldosterone-treated group, spironolactone-treated group, and corresponding control group; and C is the statistical graph of IKB-α, Pp65, IL-1, TNF-α, and IL-3 levels in the aldosterone-treated group and spironolactone-treated group.

[0050] Figure 5 These are the results of the detection of lactate content in astrocytes and lactate metabolism-related receptors. The upper figure is a statistical graph of the lactate content in different groups in lumbar spinal cord tissue, and the lower figure is the fluorescence detection results and statistical results of lactate metabolism-related receptors MCT1, MCT2, and MCT4.

[0051] Figure 6 These are the fluorescence detection results of lactate metabolism-related receptors MCT1, MCT2, and MCT4 after blocking the NF-KB signaling pathway in the aldosterone group and the aldosterone + JSH-23 group.

[0052] Figure 7 Figure 3 shows the aldosterone levels and adrenal morphology results in ALS patients and healthy controls. A is a representative image of adrenal gland volume enlargement with nodular hyperplasia in ALS patients, B is a representative image of adrenal gland in normal controls, C is a statistical graph of adrenal gland volume in ALS patients and normal controls, and D is a statistical graph of serum aldosterone levels in ALS patients and normal controls.

[0053] Figure 8 This is the ROC curve for aldosterone in diagnosing ALS. DETAILED DESCRIPTION

[0054] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making any creative efforts shall fall within the scope of protection of the present invention.

[0055] Example

[0056] 1. Materials and Methods

[0057] 1. Study Cohort

[0058] 1) Animal sample sources: B6SJL-BTg(SOD1-G93A)1Gur / J hemizygous male mice and B6SJLF1 / J + / + The female mice were bred, that is, the SOD1 carrying the mutant human SOD1 gene containing the amino acid substitution Gly93→Ala was introduced into the female mice. G93A Transgenic mice were bred on a B6 / SJL background. Genomic DNA was extracted from mice at 30 days of age and identified using PCR amplification. Genotyping of mice was performed by PCR using DNA extracted from tail tissue. Throughout the study, mice were housed under a 12:12 hr light-dark cycle with controlled temperature and humidity. Food and water were provided twice weekly to ensure that mice had free access to adequate food and water at all times.

[0059] 2) Source of clinical samples: Clinical patient samples were obtained from the Department of Neurology, The Second Hospital of Hebei Medical University. According to the El Escorial criteria, all patients were diagnosed with definite or probable amyotrophic lateral sclerosis. Based on a negative family history, patients were considered to have sporadic ALS (sALS). Complex diseases, such as hypertension and heart failure, can affect the activity of the renin-angiotensin-aldosterone system; therefore, patients with diseases such as hypertension that affect the adrenal axis were excluded; and age- and sex-matched healthy controls were selected. This study was reviewed by the Ethics Committee of The Second Hospital of Hebei Medical University, and the health, rights, and privacy of patients were fully protected; potential risks and harm to subjects could be minimized.

[0060] 2. Behavioral Analysis

[0061] Starting from 60 days of age, motor function was assessed weekly using a rotarod apparatus. As performance criteria, we chose 180 seconds as the maximum cutoff time at a speed of 16 rpm. Each mouse was tested in triplicate, and the maximum value was recorded. Footprint analysis was performed at 110 days of age. Onset was determined when the mouse was unable to run for 180 seconds. End-stage (ES) was defined when the mouse was unable to regain a standing position within 30 seconds after lying on its back.

[0062] 3. Immunochemistry

[0063] Mice were deeply anesthetized with a lethal dose of chloral hydrate and then fixed by transcardial perfusion with saline and 4% paraformaldehyde. The lumbar enlargement (lumbar segment 1 to sacral segment 3) was isolated from the spinal cord and sliced ​​into 18-μm-thick sections using a Leica vibratome. The sections were then incubated in TBS supplemented with 0.025% Triton-X100 and 10% horse serum for 2 hours at room temperature. Samples were incubated for 72 hours at 4°C with primary antibodies: GFAP (Wako, Tokyo, Japan), NeuN (Millipore, Billerica, MA, USA), MCT1 (Proteintech, Wuhan, China), MCT2 (Proteintech, Wuhan, China), and MCT4 (Proteintech, Wuhan, China), followed by incubation with fluorescent secondary antibodies for 2 hours at room temperature. All images were acquired using a fluorescence confocal microscope (Zeiss LSM-900, Germany).

[0064] 4. Western Blot Analysis

[0065] Lumbar spinal cord tissue samples were snap-frozen in liquid nitrogen, homogenized by sonication at 4°C, and then centrifuged in a microcentrifuge (10,000 g for 10 minutes at 4°C). Western blotting was performed using 50 μg of total protein. Equal amounts of protein were separated by 6%–12% SDS-PAGE gels and transferred to PVDF membranes (Immobilon-P, Millipore Bedford, MA, USA). The membranes were blocked with 5% nonfat milk for 1 hour at room temperature and incubated overnight at 4°C with the appropriate primary antibodies (anti-CD11b (Proteintech), GFAP (Millipore), Phospho-p65 (Proteintesh), IKB-α (Proteinteech), and β-actin (Santa Cruz)). The membranes were washed three times with PBS-T for 10 minutes each and then incubated with secondary antibodies for 2 hours at room temperature. The images were analyzed using an Odyssey infrared imaging system (LI-COR, Lincoln, NE, USA). Immunoreactive protein intensities were measured using ImageJ software and normalized to β-actin levels. All experiments were repeated at least three times.

[0066] 5. Enzyme-linked immunosorbent assay (ELISA)

[0067] Tissues were collected from sacrificed mice and transferred to test tubes. Blood samples (5 ml) were collected from ALS patients and healthy controls. All samples were then centrifuged at 2500 rpm for 10 minutes, and the supernatants were stored at −80°C until use. ELISA kits for aldosterone, lactate, IL-1β, TNF-α, and IL-3 were purchased from DAKEWE (Shenzhen, China), and all ELISAs were performed according to the manufacturer's protocols.

[0068] 6. Statistical analysis

[0069] The results were analyzed using Student's t test or one-way analysis of variance followed by Student-Newman-Keuls test or Dunn's t test. Statistical significance was set at P < 0.05.

[0070] 2. Experimental Results

[0071] 1. SOD1 G93A Significant differences in aldosterone levels and adrenal gland morphology between mice and B6 mice

[0072] SOD1 G93A Mice (ALS mice) and B6 mice were collected, and the changes in aldosterone content were detected by ELISA. Figure 1Figure A shows that the aldosterone content in the lumbar spinal cord tissue of ALS mice increased significantly during the onset stage, while the aldosterone content decreased significantly during the end-stage stage. Figure 1 B). HE staining revealed that as the disease progressed, the adrenal gland structure and cell morphology of mice changed significantly. The adrenal cells of terminal mice atrophied and became loosely arranged. Figure 1 As shown in CH.

[0073] 2. Aldosterone receptor antagonists delay the onset of ALS

[0074] To verify whether aldosterone is associated with the progression of ALS, ALS mice were divided into an experimental group and a control group. The experimental group mice were given aldosterone and an aldosterone receptor antagonist (spironolactone), respectively, while the control group mice were given normal saline. Figure 2 As shown, it was observed that the onset of the disease in the mice given aldosterone was significantly advanced and their motor function decreased; while the onset of the disease in the mice given spironolactone was significantly delayed.

[0075] 3. Levels of inflammatory factors in the lumbar cord tissue of ALS mice in the aldosterone-treated group

[0076] ALS mice of the same littermate were used as controls. The aldosterone-administered group was given aldosterone until the onset of disease in the aldosterone-administered group, and the lumbar cord tissue of the mice was obtained. The spironolactone-administered group was given spironolactone until the onset of disease in the control group, and the lumbar cord tissue of the mice was obtained. The control groups were all given corresponding solvents. Immunochemistry and protein blotting detection showed that the levels of inflammatory cytokines (GFAP, CD11b, IKB-α) in the lumbar cord tissue of ALS mice administered with aldosterone increased, and astrocytes and microglia were activated. The levels of inflammatory cytokines (GFAP, CD11b, Pp65, IL-1, TNF-α, IL-3) in the lumbar cord tissue of mice in the spironolactone group were reduced, and the number of activated astrocytes and microglia was reduced. The results are as follows Figure 3-4 As shown in the figure, it can be observed that astrocytes in the aldosterone group were activated, while the astrocytes in the control group were activated to a lesser extent. Astrocytes in the spironolactone group were activated to a lesser extent, while astrocytes in the control group were activated.

[0077] 4. Detection of lactate content in astrocytes

[0078] The results showed that the lactic acid content in the lumbar spinal cord tissue of ALS mice gradually decreased as the disease progressed. The mice were divided into spironolactone group and aldosterone group. The experiment found that the lactic acid content in the lumbar spinal cord tissue of ALS mice treated with spironolactone was significantly higher than that of the aldosterone group. Immunofluorescence detection found that the content of lactic acid metabolism-related receptors MCT1, MCT2, and MCT4 in the spironolactone group was higher than that in the aldosterone group. Figure 5shown.

[0079] To further investigate the pro-inflammatory effects of aldosterone (possibly through the activation of the NF-κB pathway) on astrocyte lactate metabolism, ALS mice were divided into an aldosterone group and an aldosterone + JSH-23 (NF-κB inhibitor) group. Figure 6 As shown in the fluorescence images, red represents astrocytes and neurons, respectively. Green represents the MCT marker. MCT1 / MCT4 correspond to astrocytes, and MCT2 corresponds to neurons. Blocking the NF-κB signaling pathway observed an increase in the levels of lactate metabolism-related receptors MCT1, MCT2, and MCT4 in ALS mice compared to the aldosterone group, demonstrating improved lactate metabolism.

[0080] 5. Testing clinical patient samples to verify the diagnostic value of aldosterone

[0081] The researchers collected serum from 30 ALS patients and 30 healthy controls from the Department of Neurology, Hebei Medical University Second Hospital, and tested the changes in aldosterone levels. They found that the aldosterone levels in ALS patients were significantly higher than those in the healthy control group. They also tested the changes in the adrenal gland volume in ALS patients and found that the adrenal gland volume in ALS patients was significantly increased and accompanied by nodular hyperplasia. Figure 7 As shown. The ROC curve is calculated based on clinical samples as shown Figure 8 As shown, the AUC value of aldosterone for diagnosing ALS was 0.8488, and its 95% confidence interval was 0.7179-0.9796, indicating that aldosterone can be used as an independent diagnostic marker for ALS with good diagnostic efficacy.

[0082] 6. Treatment of ALS patients with aldosterone receptor antagonists

[0083] Ten ALS patients were enrolled and observed for four months, taking one spironolactone tablet orally every two days. Three discontinued medication due to low blood pressure. Of the remaining seven, three experienced increased muscle strength (one was able to sit up from a recumbent position, and two experienced increased lower limb muscle strength and walking distance). The remaining four patients have shown no disease progression since starting medication.

[0084] The above embodiments are only provided for understanding the method and core concept of the present invention. It should be noted that, without departing from the principles of the present invention, a number of improvements and modifications may be made to the present invention by a person skilled in the art, and such improvements and modifications shall fall within the scope of protection of the claims of the present invention.

Claims

1. Use of a reagent for detecting aldosterone levels in a sample in the preparation of a product, characterized in that: The product is used for in vitro diagnosis, auxiliary diagnosis and / or disease monitoring of amyotrophic lateral sclerosis.

2. The use according to claim 1, characterized in that The reagent for detecting the aldosterone level in the sample detects the aldosterone level in the sample by one or more of the following methods: radioimmunoassay, chemiluminescence assay, enzyme-linked immunosorbent assay, chromatography, spectroscopy, mass spectrometry, chromatography-mass spectrometry; Preferably, the product includes a kit and a chip.

3. The use according to claim 1, characterized in that The sample includes serum, plasma, urine, blood, tissue or cell culture fluid.

4. A product for diagnosing or assisting in the diagnosis of amyotrophic lateral sclerosis and / or monitoring the condition of patients with amyotrophic lateral sclerosis, characterized in that: The product includes a reagent for detecting the level of aldosterone in a sample; Preferably, the product includes a kit and a chip.

5. The product according to claim 4, characterized in that The reagent for detecting the aldosterone level in the sample detects the aldosterone level in the sample by one or more of the following methods: radioimmunoassay, chemiluminescence assay, enzyme-linked immunosorbent assay, chromatography, spectroscopy, mass spectrometry, chromatography-mass spectrometry; Preferably, the sample comprises serum, plasma, urine, blood, tissue or cell culture fluid; Preferably, the product further comprises reagents for processing the sample.

6. Use of an aldosterone receptor antagonist in the preparation of a drug for treating amyotrophic lateral sclerosis, characterized in that: The aldosterone receptor antagonists include spironolactone, eplerenone, and finerenone; Preferably, the aldosterone receptor antagonist is spironolactone.

7. Use of aldosterone as a target in screening drugs for preventing or treating amyotrophic lateral sclerosis, characterized in that: The screening involves determining whether a drug is a candidate drug for preventing or treating amyotrophic lateral sclerosis based on its effects on aldosterone before and after use.

8. A computer-implemented method for constructing an amyotrophic lateral sclerosis diagnostic model, characterized in that: The method comprises the following steps: obtaining aldosterone expression level data of ALS patients and healthy controls, and constructing a diagnostic model based on the expression level data; Preferably, the diagnostic model predicts whether a subject has amyotrophic lateral sclerosis, whether a subject is at risk of developing amyotrophic lateral sclerosis, or monitors disease progression in a subject with amyotrophic lateral sclerosis based on aldosterone level data in a sample; Preferably, the construction of the diagnostic model based on the expression level data is performed by algorithmic model construction; Preferably, the algorithm includes one or more of a linear regression model, a logistic regression model, a Lasso regression model, a Ridge regression model, a linear discriminant analysis model, a nearest neighbor model, a decision tree model, a perceptron model, a neural network model, a support vector machine model, a naive Bayes model, an AdaBoost model, a GBDT model, an XGBoost model, a LightGBM model, a CatBoost model or a random forest model.

9. A computer-implemented system for diagnosing and / or monitoring amyotrophic lateral sclerosis, characterized in that: The system comprises: Data acquisition unit: obtaining aldosterone level data in samples; A data classification unit: inputting the aldosterone level data into a constructed diagnostic model, wherein the diagnostic model is constructed based on the method according to claim 8; Output unit: outputs and stores analysis results, indicating whether the subject has amyotrophic lateral sclerosis, whether the subject has a risk of developing amyotrophic lateral sclerosis, or monitors the disease progression of a subject with amyotrophic lateral sclerosis.

10. A computer device for diagnosing and / or monitoring amyotrophic lateral sclerosis, characterized in that: The computer device comprises: a processor adapted to implement the instructions; and A memory adapted to store a plurality of instructions adapted to be loaded by a processor and executed by the processor: Acquire data, obtain aldosterone level data in the sample; Processing the data, inputting the aldosterone level data into a constructed diagnostic model, wherein the diagnostic model is constructed based on the method of claim 8; Outputting a result: Outputting and storing an analysis result, indicating whether the subject has amyotrophic lateral sclerosis, whether the subject is at risk of developing amyotrophic lateral sclerosis, or monitoring the progression of the disease in a subject with amyotrophic lateral sclerosis.

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