Application of a strain of Lactobacillus plantarum in the prevention and treatment of Alzheimer's disease

Abstract

This application provides a strain of Lactobacillus plantarum HLP0106, and the use of this strain or its fermentation products in the prevention and / or treatment of Alzheimer's disease.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to a type of Lactobacillus plantarum, and the application of the strain or its fermentation products in the prevention and / or treatment of Alzheimer's disease. Background Technology

[0002] Alzheimer's disease (AD) is the most common cause of dementia and the sixth leading cause of death worldwide. AD is a progressive neurodegenerative disease characterized by early, mild spontaneous cognitive impairment and later, severe neurological and psychiatric damage, including impairments in executive function, attention, and language. Known neuropathological features of AD include extracellular neuritis plaques composed of aggregated β-amyloid (Aβ), neurofibrillary tangles composed of aggregated hyperphosphorylated tau protein, gliosis, and neuronal loss. Currently, drugs designed to target the pathological features of Alzheimer's disease, such as anti-Aβ antibodies, anti-Tau antibodies, or cholinesterase inhibitors (e.g., donepezil, rivastigmine), can only help improve the quality of life and extend life expectancy of AD patients. They cannot stop the progression of AD. Summary of the Invention

[0003] Through extensive screening and activity studies, the inventors of this application isolated a strain of Lactobacillus plantarum HLP0106 ​​from healthy volunteers. In Alzheimer's disease model mice, it exhibited multidimensional effects such as cognitive improvement, muscle function maintenance, mood regulation, and working memory protection. Moreover, its effects were significantly superior to the currently commercially available popular probiotic strains of the same genus, PS128 and UA1290, demonstrating unique application potential in the prevention and treatment of Alzheimer's disease.

[0004] Therefore, in one respect, this application provides *Lactobacillus plantarum* (… Lactiplantibacillus plantarum HLP0106 ​​was deposited on May 21, 2025, at the China General Microbiological Culture Collection Center (CGMCC) with accession number CGMCC No. 34611.

[0005] On the other hand, this application provides progeny of *Lactobacillus plantarum* HLP0106 ​​as described above.

[0006] In some embodiments, the progeny of *Lactobacillus plantarum* HLP0106 ​​is a passaged culture of *Lactobacillus plantarum* HLP0106, for example, a passaged culture of up to 5, 10, 20, 30, or 40 generations.

[0007] In some embodiments, the progeny of *Lactobacillus plantarum* HLP0106 ​​has at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least 99.9%, or at least 99.99% sequence identity with the genome of *Lactobacillus plantarum* HLP0106.

[0008] In some embodiments, the progeny of *Lactobacillus plantarum* HLP0106 ​​retain the preventive and / or therapeutic activity of *Lactobacillus plantarum* HLP0106 ​​for Alzheimer's disease.

[0009] As used herein, the term "identity" refers to the sequence matching between two polypeptides or two nucleic acids. Two compared sequences are identical at a position when the same base or amino acid monomeric subunit occupies the same location (e.g., a position in each of two DNA molecules is occupied by adenine, or a position in each of two polypeptides is occupied by lysine). The "percentage identity" between two sequences is a function of the number of matching positions shared by the two sequences divided by the number of positions compared × 100. For example, if six out of ten positions in two sequences match, then the two sequences have 60% identity. For example, the DNA sequences CTGACT and CAGGTT share 50% identity (three out of six positions match). Typically, two sequences are compared to produce the maximum identity. Such comparisons can be made using methods readily available, for example, computer programs such as the Align program (DNAstar, Inc.) Needleman et al. (1970) J. Mol. Biol. 48: 443-453. The percentage identity between two amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl Biosci., 4:11-17 (1988)) integrated into the ALIGN program (version 2.0), which uses a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4. Alternatively, the percentage identity between two amino acid sequences can be determined using the Needleman and Wunsch algorithm (J MoIBiol. 48:444-453 (1970)) in the GAP program integrated into the GCG software package (available at www.gcg.com), which uses a Blossum 62 matrix or a PAM250 matrix, along with gap weights of 16, 14, 12, 10, 8, 6, or 4, and length weights of 1, 2, 3, 4, 5, or 6.

[0010] On the other hand, this application provides fermentation products of *Lactobacillus plantarum* HLP0106 ​​or its progeny as described above.

[0011] As used herein, the term "fermentation product" refers to all substances synthesized and / or secreted by a specific bacterial strain through metabolic pathways during its growth and reproduction, when the strain is inoculated into a suitable culture medium and cultured under certain fermentation conditions (such as temperature, pH, dissolved oxygen, time, etc.). This includes primary metabolites, secondary metabolites, and other extracellular products. It also covers products obtained after processing fermentation broth or its components containing the above substances through conventional post-processing procedures such as centrifugation, filtration, concentration, extraction, and drying. In some cases, fermentation products may also contain bacterial cells or their cellular components.

[0012] On the other hand, this application provides the use of *Lactobacillus plantarum* HLP0106 ​​or its progeny, or the fermentation product of said *Lactobacillus plantarum* HLP0106 ​​or its progeny, as described above, in the preparation of a product for the prevention and / or treatment of Alzheimer's disease in subjects.

[0013] In some implementations, the product is a drug, health product, or food.

[0014] In some implementations, the product is administered to the subject orally.

[0015] In some implementations, the product is a microbial agent.

[0016] In some embodiments, the microbial agent comprises *Lactobacillus plantarum* HLP0106 ​​in live cell form and / or its progeny.

[0017] In some embodiments, the microbial agent contains at least 5 × 10⁻⁶ 7 CFU / g (e.g., at least 1×10⁻⁶) 8 CFU / g, at least 5×10 8 CFU / g, at least 1×10 9 CFU / g, at least 5×10 9 CFU / g, at least 1×10 10 CFU / g, at least 1×10 11 CFU / g, at least 3×10 11 CFU / g, at least 1×10 12 The plant lactobacillus HLP0106 ​​and / or its progeny (CFU / g).

[0018] In some embodiments, the microbial agent further comprises strains selected from Lactobacillus reuteri, Bifidobacterium, Bifidobacterium longum, Lactobacillus rhamnosus, and any combination thereof.

[0019] In some embodiments, the product is administered in combination with other components (e.g., pharmaceutically active agents) that have activity in preventing and / or treating Alzheimer's disease, for example, separately or in combination, simultaneously or sequentially.

[0020] In some implementations, the product is used for one or more of the following: (i) Improve muscle aging in subjects (e.g., Alzheimer's patients); (ii) Improve the anxiety of subjects (e.g., Alzheimer's patients); (iii) Improve working memory impairment in subjects (e.g., patients with Alzheimer's disease); (iv) Improve spatial learning impairments in subjects (e.g., Alzheimer's patients); (v) Improve long-term memory retention in subjects (e.g., Alzheimer's disease patients).

[0021] In some implementations, the subject is a mammal, such as a human.

[0022] On the other hand, this application provides a method for preventing and / or treating Alzheimer's disease in a subject, comprising administering to the subject in need an effective amount of the above-described Lactobacillus plantarum HLP0106 ​​or its progeny, or the above-described fermentation product of Lactobacillus plantarum HLP0106 ​​or its progeny.

[0023] In some embodiments, the *Lactobacillus plantarum* HLP0106 ​​or its progeny, and the fermentation product, are administered to the subject orally.

[0024] In some embodiments, the *Lactobacillus plantarum* HLP0106 ​​or its progeny is administered to the subject in the form of a bacterial agent.

[0025] In some embodiments, the microbial agent comprises *Lactobacillus plantarum* HLP0106 ​​in live cell form and / or its progeny.

[0026] In some embodiments, the microbial agent contains at least 5 × 10⁻⁶ 7 CFU / g (e.g., at least 1×10⁻⁶) 8 CFU / g, at least 5×10 8 CFU / g, at least 1×10 9 CFU / g, at least 5×10 9 CFU / g, at least 1×10 10 CFU / g, at least 1×10 11 CFU / g, at least 3×10 11 CFU / g, at least 1×10 12The plant lactobacillus HLP0106 ​​and / or its progeny (CFU / g).

[0027] In some embodiments, the microbial agent further comprises strains selected from Lactobacillus reuteri, Bifidobacterium, Bifidobacterium longum, Lactobacillus rhamnosus, and any combination thereof.

[0028] In some embodiments, the *Lactobacillus plantarum* HLP0106 ​​or its progeny, the fermentation product, and other components with preventive and / or therapeutic activity against Alzheimer's disease (e.g., pharmaceutically active agents) are administered in combination, for example, separately or in combination, simultaneously or sequentially.

[0029] In some implementations, the method is used for one or more of the following: (i) Improve muscle aging in subjects (e.g., Alzheimer's patients); (ii) Improve the anxiety of subjects (e.g., Alzheimer's patients); (iii) Improve working memory impairment in subjects (e.g., patients with Alzheimer's disease); (iv) Improve spatial learning impairments in subjects (e.g., Alzheimer's patients); (v) Improve long-term memory retention in subjects (e.g., Alzheimer's disease patients).

[0030] In some implementations, the subject is a mammal, such as a human.

[0031] On the other hand, this application provides a microbial agent comprising live cell form of *Lactobacillus plantarum* HLP0106 ​​and / or its progeny as described above.

[0032] In some embodiments, the microbial agent comprises at least 5 × 10⁻⁶. 7 CFU / g (e.g., at least 1×10⁻⁶) 8 CFU / g, at least 5×10 8 CFU / g, at least 1×10 9 CFU / g, at least 5×10 9 CFU / g, at least 1×10 10 CFU / g, at least 1×10 11 CFU / g, at least 3×10 11 CFU / g, at least 1×10 12 The plant lactobacillus HLP0106 ​​and / or its progeny (CFU / g).

[0033] In some embodiments, the microbial agent further comprises strains selected from Lactobacillus reuteri, Bifidobacterium, Bifidobacterium longum, Lactobacillus rhamnosus, and any combination thereof.

[0034] In another aspect, this application provides a pharmaceutical composition comprising *Lactobacillus plantarum* HLP0106 ​​or its progeny as described above, or a fermentation product of *Lactobacillus plantarum* HLP0106 ​​or its progeny.

[0035] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and / or excipient.

[0036] In some embodiments, the pharmaceutical composition further comprises additional components (e.g., pharmaceutically active agents) having activity in preventing and / or treating Alzheimer's disease.

[0037] On the other hand, this application provides the use of *Lactobacillus plantarum* HLP0106 ​​or its progeny as described above in the construction of engineered strains for the prevention and / or treatment of Alzheimer's disease.

[0038] Beneficial effects of the invention

[0039] The *Lactobacillus plantarum* strain HLP0106 ​​provided in this application exhibits multidimensional improvement effects in Alzheimer's disease model mice, including but not limited to improvements in cognitive function, maintenance of muscle function, mood regulation, and protection of working memory. Therefore, strain HLP0106 ​​possesses unique technical value in the prevention and treatment of Alzheimer's disease and shows significant potential for clinical application.

[0040] Furthermore, through parallel comparative studies, the inventors of this application found that, compared with the currently commercially available popular probiotic strains of the same genus *Lactobacillus plantarum*, PS128 and UA1290, the strain HLP0106 ​​of this application showed significant superiority in improving multiple symptoms related to Alzheimer's disease.

[0041] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings and examples. However, those skilled in the art will understand that the following drawings and examples are for illustrative purposes only and are not intended to limit the scope of the invention. Various objects and advantages of the present invention will become apparent to those skilled in the art from the following detailed description of the drawings and preferred embodiments.

[0042] Instructions on the Preservation of Biological Materials

[0043] This invention relates to the following biological materials that have been deposited at the China General Microbiological Culture Collection Center (CGMCC): Lactobacillus plantarum ( Lactiplantibacillus plantarumHLP0106, which has accession number 34611 and accession date of May 21, 2025. Attached Figure Description

[0044] Figure 1A : Body weight of mice in each group.

[0045] Figure 1B Grip strength of mice in each group.

[0046] Figure 1C The ratio of grip strength to body weight in each group of mice.

[0047] Figure 2A Total distance traveled by mice in each group during the open field experiment.

[0048] Figure 2B : Percentage of time each group of mice spent in the central region during the open field experiment.

[0049] Figure 3A The total number of times mice in each group entered each arm in the Y-maze spontaneous alternation experiment.

[0050] Figure 3B Spontaneous alternation rate of mice in each group during the Y-maze experiment.

[0051] Figure 4A : The escape latency of mice in each group on the first day in the Morris water maze experiment.

[0052] Figure 4B In the Morris water maze experiment, the escape latency of mice in each group was 2-5 days.

[0053] Figure 5A In the Morris water maze experiment, the percentage of the distance that mice in each group swam in the quadrant where the platform was located.

[0054] Figure 5B In the Morris water maze experiment, the percentage of time each group of mice spent swimming in the quadrant where the platform was located. Detailed Implementation

[0055] The invention will now be described with reference to the following embodiments, which are intended to illustrate the invention (and not limit it). Those skilled in the art will appreciate that the embodiments are described by way of example and are not intended to limit the scope of protection claimed by the invention.

[0056] Example 1: Screening of *Lactobacillus plantarum* (also referred to herein as *Lactobacillus plantarum*) in this application

[0057] 1. Sample processing

[0058] Healthy human feces were used. The anaerobic chamber was filled with an anaerobic gas mixture (85% N2 / 10% CO2 / 5% H2) the day before the experiment. Fecal samples stored at -80°C were removed and transferred to the pre-prepared anaerobic chamber as soon as possible. After two hours of anaerobic treatment, the fecal samples were dissolved and suspended in pre-anaerobic YCFA medium. To prevent clogging of the microfluidic chip, the bacterial suspension was filtered through a 40 μm sterile filter membrane to remove large food residues and particles.

[0059] 2. Single-cell encapsulation

[0060] The treated fecal samples were diluted with PBS, and the diluted bacterial suspension was used as the dispersed phase, while light mineral oil was used as the continuous phase. After evaluating and optimizing parameters such as flow rate and cell loading density, the system achieved stable and uniform droplet formation and single-cell encapsulation. Droplets were collected in Eppendorf tubes filled with mineral oil to prevent droplet breakage. Microfluidic operations were performed in an anaerobic chamber.

[0061] The concentration of the droplets in the collection tube was measured using a microscope and adjusted to approximately 6.0 × 10⁻⁶ per microliter using mineral oil. 4 Droplets. Since approximately 1% of the droplets were single-cell droplets, and the remainder were empty droplets, 10 µL of droplet / oil solution was removed from the Eppendorf tube and plated onto an agar plate, then incubated in an anaerobic incubator for 72 hours. Similarly, 10 µL of 6.0 × 10⁻⁶ droplets / oil solution was... 5 Cell solutions of live cells / mL were spread in parallel on agar plates and incubated in an anaerobic chamber for 72 hours. YCFA plates were used, with three replicates for each condition.

[0062] 3. Identifying probiotics with potential functions

[0063] 3.1. Preservation of microbial strains

[0064] Remove the agar plate from the 37°C incubator, pick a single colony from the agar plate, transfer it to 4 mL of YCFA liquid medium, and incubate at 37°C for 24 hours to enrich the colony. Label the colony. Then, add 300 μL of 70% glycerol and 700 μL of the enriched bacterial solution to cryovials, label them, and store two tubes of each bacterial solution at -80°C for subsequent experiments. The remaining enriched bacterial solutions will be used for 16S rRNA sequencing to determine the bacterial strain.

[0065] 3.2. 16S rRNA gene sequencing

[0066] The 16S rRNA sequencing of the isolated bacteria was performed by Suzhou Genewiz Biotechnology Co., Ltd. The preserved bacterial cultures were sequenced for 16S rRNA to identify the bacterial strains. Genomic DNA was extracted from each single-cell colony using the TIANamp Bacteria DNA Kit, and then the full-length 16S rRNA gene fragment was amplified by polymerase chain reaction using universal primers 27F (5′-AGAGTTGATCCTGGCTCAG-3′, SEQ ID NO: 1) and 1492R (5′-GGTTACCTTGTTACGACTT-3′, SEQ ID NO: 2).

[0067] PCR reactions were performed in a 50 μL system containing 2 μL upstream primer, 2 μL downstream primer, 25 μL 2x Phanta Max Buffer, 17 μL ddH2O, 1 μL Phanta Max Super-Fidelity DNA polymerase, 1 μL dNTP Mix, and 2 μL DNA template. PCR amplification was performed as follows: initial denaturation at 95°C for 10 min, followed by 40 cycles of 95°C (30 s), 57.3°C (1 min), and 72°C (30 s), with a final extension at 72°C for 5 min. The target PCR product was confirmed by agarose gel electrophoresis, purified using the QIAquick Gel Extraction Kit, and sequenced using Sanger sequencing to obtain the gene sequence. Finally, the 16S rRNA sequence of the strain was compared with sequences in the GenBank database using the NCBI database, and species identification was performed using BLAST. The species with the highest sequence similarity was selected for identification. When the gene sequence of the tested strain has more than 99% homology with the gene sequence in the database, it can be considered to be the same species.

[0068] 3.3. A highly active strain of Lactobacillus plantarum HLP0106 ​​was screened using the above methods. It has been deposited at the China General Microbiological Culture Collection Center (CGMCC) with accession number CGMCC 34611.

[0069] Example 2: Lactobacillus plantarum for the treatment of Alzheimer's disease

[0070] 1. Experiment Overview

[0071] This study systematically evaluated the effect of HLP0106 ​​intervention on cognitive function by constructing an Alzheimer's disease (AD) mouse model. Five × FAD transgenic mice (purchased from Cyagen (Suzhou) Biotechnology Co., Ltd., catalog number: C001270) were used in the experiment. The mice were divided into four groups: HLP0106 ​​intervention group (AD+HLP0106), commercial Lactobacillus plantarum PS128 intervention group (AD+PS128), commercial Lactobacillus plantarum UA1290 intervention group (AD+UA1290), model control group (AD+PBS), and wild-type control group (WT+PBS, where healthy mice were used as the wild-type control group). Mice in the strain intervention groups were supplemented with the corresponding probiotics via gavage at a dose of 2 × 10⁻⁶. 8 CFU / time / day, control mice were given the same volume of PBS, and after 12 weeks of continuous intervention, the following behavioral tests were performed in sequence: (1) grip strength test (to assess muscle aging); (2) open field test (to assess anxiety level); (3) Y maze spontaneous alternation test (to assess working memory and spatial exploration); (4) Morris water maze (to assess spatial learning and memory).

[0072] The strains PS128 and UA1290 used in this embodiment are both commercially available Lactobacillus plantarum probiotics. PS128 was purchased from Shanghai Lianya Probiotics Technology Co., Ltd., catalog number: 51326012701; UA1290 was purchased from Sichuan Fuyuan Energy Biotechnology Co., Ltd., catalog number: 669ELO11.

[0073] 2. Results of the behavioral experiment

[0074] 2.1 Grip strength test

[0075] In the grip strength test, all five groups of mice were well-developed, and there was no statistically significant difference in body weight. The grip strength of the AD model control group mice was significantly lower than that of the wild-type control group, suggesting that their muscle aging was more pronounced. This result was also verified by the grip strength to body weight ratio. After intervention with HLP0106 ​​*Lactobacillus plantarum*, the muscle aging phenotype in AD mice was alleviated, while commercially available *Lactobacillus plantarum* PS128 and UA1290 did not show similar improvement. Figure 1A-1C ).

[0076] 2.2. Open Field Experiment

[0077] In the open field experiment (the results are as follows) Figure 2A-2BThe total movement distance of the five groups of mice showed no statistically significant difference, indicating that the motor abilities of the mice in each group were basically the same. Compared with wild-type mice, the percentage of time spent in the central region by the AD model control group was significantly reduced, suggesting a significant increase in their anxiety level. The percentage of time spent in the central region by the HLP0106 ​​*Lactobacillus plantarum* intervention group was significantly increased compared with the AD model control group, indicating that this strain can effectively alleviate anxiety-like behavior in AD mice; while the intervention effects of commercial *Lactobacillus plantarum* PS128 and UA1290 were not significant.

[0078] 2.3 Spontaneous Alternation Experiment in the Y-maze

[0079] In the spontaneous alternation test of the Y maze (the results are as follows) Figures 3A-3B The total number of arm insertions was not significantly different among the groups, indicating that their autonomous exploration ability and motor function were basically consistent; however, the HLP0106 ​​intervention group showed a slightly higher total number of arm insertions. Compared with the wild-type control group, the spontaneous alternation rate of the Alzheimer's disease model mice was significantly reduced, suggesting that they had spatial working memory impairment related to hippocampal function. After HLP0106 ​​intervention, the spontaneous alternation rate of the model mice was significantly improved, indicating that HLP0106 ​​can effectively improve their working memory dysfunction; however, the improvement effect of the commercial Lactobacillus plantarum PS128 and UA1290 intervention groups was not as good as that of HLP0106.

[0080] 2.4 Morris Water Maze

[0081] 2.4.1 Escape incubation period

[0082] During the five-day positioning and navigation training (the results are as follows) Figures 4A-4B The average escape latency of the AD group mice was significantly higher than that of the wild-type control group, indicating a significant deficiency in their spatial learning ability. Compared with the AD group, the PS128 intervention group, and the UA1290 intervention group, HLP0106 ​​intervention significantly shortened the escape latency of the mice, demonstrating that HLP0106 ​​intervention can effectively alleviate spatial learning impairment.

[0083] 2.4.2 Exploration of the Target Quadrant

[0084] In space exploration experiments (results as follows) Figures 5A-5B Compared with the wild-type control group, AD model mice showed significantly reduced time spent and distance traveled in the target quadrant, indicating a severe deficit in long-term spatial memory. HLP0106 ​​intervention significantly increased exploration activity in this quadrant, demonstrating its effective promotion of long-term memory retention of platform locations. The improvement effects of commercial Lactobacillus plantarum PS128 and UA1290 interventions were less than those of HLP0106.

[0085] 3. Experimental Conclusions

[0086] This series of behavioral experiments consistently demonstrates that intervention with HLP0106 ​​*Lactobacillus plantarum* significantly improves multidimensional cognitive functions in AD model mice, including muscle aging, anxiety-like behavior, working memory, and spatial learning and memory. This behavioral phenotypic validation of the feasibility and effectiveness of this strain in treating Alzheimer's disease validates its efficacy. Furthermore, through parallel comparative experiments, the HLP0106 ​​strain provided in this application showed significantly superior performance compared to currently commercialized *Lactobacillus plantarum* PS128 and UA1290 in improving multiple aspects of AD symptoms.

[0087] 4. Comparative analysis of the strain of this invention with the prior art strain PS128

[0088] 4.1 The PS128 has superior performance compared to existing technologies.

[0089] Lactobacillus plantarum PS128 is a recognized "psychiatric probiotic" strain with outstanding probiotic effects. Existing research shows that PS128 can improve symptoms of neuropsychiatric disorders through multiple pathways, including regulating gut microbiota, short-chain fatty acid levels, and neuroinflammation. Specifically, the study by Huang et al. (2021) confirmed... 2 PS128 intervention effectively prevented cognitive impairment in Alzheimer's disease model mice, and its mechanism of action involved regulating propionic acid levels, inhibiting glycogen synthase kinase 3β activity, and reducing glial proliferation. Furthermore, PS128 also showed effects in Parkinson's disease. 3 autism 4 and depression 5 It has also been shown to have significant improving effects in models of central nervous system diseases. Therefore, PS128 can be used as a benchmark control strain to measure the efficacy of Lactobacillus plantarum in the treatment of Alzheimer's disease and related neuropsychiatric diseases.

[0090] 4.2 Technical advantages of HLP0106 ​​compared to PS128 and UA1290

[0091] Although PS128 has been shown to improve cognition in Alzheimer's disease model mice, as demonstrated by the experimental data in this application, the *Lactobacillus plantarum* HLP0106 ​​screened in this application significantly outperformed PS128 in multiple behavioral dimensions. Furthermore, the strain HLP0106 ​​in this application also showed significantly superior AD-improving effects compared to another commercially available *Lactobacillus* strain, UA1290 (also known as CCFM1290). Notably, the UA1290 strain has been reported in the prior art to produce urolithin A through microbial fermentation, thereby exerting an anti-aging effect in nematode models, suggesting its potential for anti-aging.1 However, the experimental results of this application show that UA1290's improvement effects on multiple dimensions such as muscle aging, anxiety-like behavior, working memory, and spatial learning and memory in AD mice are not as good as those of the strain HLP0106 ​​provided in this application. The specific manifestations are summarized in the table below: Table 1. Comparison of effects of strains HLP0106, PS128, and UA1290

[0092] The above comparative results demonstrate that HLP0106 ​​exhibits superior multidimensional improvement effects compared to PS128 and UA1290 in various aspects, including cognitive improvement, muscle function maintenance, mood regulation, and working memory protection. This comprehensive functional advantage cannot be expected from a simple strain replacement, highlighting the unique technical value of the strain of this invention.

[0093] Although specific embodiments of the invention have been described in detail, those skilled in the art will understand that various modifications and variations can be made to the details based on all the published teachings, and all such changes are within the scope of protection of the invention. The entire scope of the invention is given by the appended claims and any equivalents thereof.

[0094] References: 1 Zhang, M. et al. Urolithin A Produced by Novel MicrobialFermentation Possess Anti-aging Effects by Improving Mitophagy and ReducingReactive Oxygen Species in Caenorhabditis elegans. J Agric Food Chem 71,6348–6357 (2023). https: / / doi.org / 10.1021 / acs.jafc.3c01062 2 Huang, HJ et al. Lactobacillus plantarum PS128 prevents cognitive dysfunction in Alzheimer's disease mice by modulating propionicacid levels, glycogen synthase kinase 3 beta activity, and gliosis. BMC Complement Med Ther21, 259 (2021). https: / / doi.org / 10.1186 / s12906-021-03426-8 3 Liao, J. F. et al. Lactobacillus plantarum PS128 alleviatesneurodegenerative progression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models of Parkinson's disease. Brain Behav Immun 90, 26–46 (2020). https: / / doi.org / 10.1016 / j.bbi.2020.07.036 4 Chen, C. M. et al. Enhancing social behavior in an autism spectrumdisorder mouse model: investigating the underlying mechanisms ofLactiplantibacillus plantarum intervention. Gut Microbes 16, 2359501 (2024).https: / / doi.org / 10.1080 / 19490976.2024.2359501 5 Lin, S. K., Kuo, P. H., Hsu, C. Y., Chiu, Y. H. & Chen, C. H. Theeffects of Lactobacillus plantarum PS128 in patients with major depressivedisorder: an eight-week double-blind, placebo-controlled study. Asian J Psychiatr 101, 104210 (2024). https: / / doi.org / 10.1016 / j.ajp.2024.104210。

Claims

1. Lactobacillus plantarum ( Lactiplantibacillus plantarum HLP0106 ​​was deposited on May 21, 2025 at the China General Microbiological Culture Collection Center (CGMCC) with accession number 34611.

2. The progeny of Lactobacillus plantarum HLP0106 ​​of claim 1.

3. Fermentation products of Lactobacillus plantarum HLP0106 ​​of claim 1 or the progeny of claim 2.

4. Use of the Lactobacillus plantarum HLP0106 ​​of claim 1, the progeny of claim 2, or the fermentation product of claim 3 in the preparation of a product for the prevention and / or treatment of Alzheimer's disease in subjects; preferably, the product is a pharmaceutical, health product, or food.

5. The use of claim 4, wherein, The product is administered to subjects orally.

6. The use according to claim 4 or 5, wherein, The product is a microbial agent; Preferably, the microbial agent comprises *Lactobacillus plantarum* HLP0106 ​​in live cell form and / or its progeny; Preferably, the microbial agent contains at least 5 × 10⁻⁶ 7 CFU / g (e.g., at least 1×10⁻⁶) 8 CFU / g, at least 5×10 8 CFU / g, at least 1×10 9 CFU / g, at least 5×10 9 CFU / g, at least 1×10 10 CFU / g, at least 1×10 11 CFU / g, at least 3×10 11 CFU / g, at least 1×10 12 The plant lactobacillus HLP0106 ​​and / or its progeny (CFU / g); Preferably, the microbial agent further comprises strains selected from the following: Lactobacillus reuteri, Bifidobacterium, Bifidobacterium longum, Lactobacillus rhamnosus, and any combination thereof.

7. The use according to any one of claims 4-6, wherein, The product is administered in combination with other components (e.g., pharmaceutically active agents) that have activity in preventing and / or treating Alzheimer's disease.

8. A microbial agent comprising, in live cell form, Lactobacillus plantarum HLP0106 ​​of claim 1 and / or progeny of claim 2; Preferably, the microbial agent contains at least 5 × 10⁻⁶ microbial agents. 7 CFU / g (e.g., at least 1×10⁻⁶) 8 CFU / g, at least 5×10 8 CFU / g, at least 1×10 9 CFU / g, at least 5×10 9 CFU / g, at least 1×10 10 CFU / g, at least 1×10 11 CFU / g, at least 3×10 11 CFU / g, at least 1×10 12 The plant lactobacillus HLP0106 ​​and / or its progeny (CFU / g); Preferably, the microbial agent further comprises strains selected from the following: Lactobacillus reuteri, Bifidobacterium, Bifidobacterium longum, Lactobacillus rhamnosus, and any combination thereof.

9. A pharmaceutical composition comprising Lactobacillus plantarum HLP0106 ​​of claim 1, the progeny of claim 2, or the fermentation product of claim 3; Preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier and / or excipient; Preferably, the pharmaceutical composition further comprises additional components (e.g., pharmaceutically active agents) having activity in preventing and / or treating Alzheimer's disease.

10. Use of the Lactobacillus plantarum HLP0106 ​​of claim 1 or the progeny of claim 2 in the construction of engineered strains for the prevention and / or treatment of Alzheimer's disease.

Images