Abstract: Objective 　The present study aimed to observe the changes in Aβ deposition and estrogen receptor levels in the hippocampal tissue of female APP/PS1 mice with Alzheimer’s disease (AD) after receiving an ovariectomy at different ages. Methods　3-month-old APP/PS1 female mice were divided into three groups, with 20 mice in each group. Ten mice were treated with bilateral ovarian resection via abdominal surgery as the model (ovx)group. The 10 mice in the control (sham) group underwent surgery in which an equivalent volume fat was removed from the corresponding area. After 3, 4, and 5 months, APP/PS1 mice were assigned to 6-, 7-, and 8-month age groups. The cognitive function of the APP/PS1 mice of different ages was evaluated using the Morris water maze. Morphological changes to intracellular organelles in the CA1 area of the hippocampus of the two groups of mice were observed using transmission electron microscopy. Immunofluorescence staining was used to detect the deposition of Aβ in the CA1 area of the hippocampus of the two groups of mice. ELISA was used to detect the levels and contents of serum estrogen, ROS, SOD, and MDA, and Western blot was used to determine the expression levels of ERα and ERβ. Results　As the ovx group mice increased in age, their escape latency in the water maze test gradually lengthened, the deposition of Aβ in the hippocampal CA1 area increased, the mitochondrial swelling of hippocampal neurons increased, and larger amounts of lipofuscin and amyloid deposition were observed in the cytoplasm. Their serum E2 levels and SOD activity decreased, while their ROS levels and MDA contents increased, and the expression of ERα and ERβ in the hippocampal tissue decreased. Conclusions　Ovariectomy in mice with low estrogen status may exacerbate hippocampal Aβ deposition and age-dependent cognitive decline.

Abstract: Objective To observe the effects of folic acid ( FA) supplementation on the expression of Flotillin-1 and β-amyloid protein ( Aβ) -metabolism-related proteins in the brains of inflammation-stimulated Alzheimer’ s disease (AD) mice. Methods Twenty-seven 6-month-old male APP / PS1 mice were randomly divided into AD, AD+LPS, and AD+LPS+FA groups, with nine mice in each group. Nine C57BL / 6J male mice born within the same month were used as the Control group. The AD + LPS + FA group was given folic-acid-supplemented feed ( 8 mg / kg ) for 3 months of intervention, while the other three groups were fed normal feed. Lipopolysaccharide solution ( LPS, 250 μg / ( kg·d) ) was injected intraperitoneally into mice in the AD+LPS and AD+LPS+FA groups 1 week before the end of the experiment, and saline was injected into the remaining two groups. The serum inflammatory factors TNF-α and IL-6 levels and brain tissue Aβ1- 40 and Aβ1- 42 levels of mice in each group were detected by ELISA. Flotillin-1 protein expression in brain tissue was detected using Western blot, and the co-expression of Flotillin-1 and Aβ1- 42 / APP / PS1 / BACE1 in the cortical region of the brain was detected via immunofluorescence double-labeling. Results After ANOVA analysis, we found mice in the AD group had elevated serum TNF-α and IL-6 levels ( P<0. 05) , elevated levels of Aβ1- 40 and Aβ1- 42 ( P<0. 05) , increased expression of Flotillin-1 protein (P<0. 05) , and increased co-expression of Flotillin-1 and Aβ1- 42 / APP / PS1 / BACE1 in the cortical brain tissue (P<0. 05) compared with the Control group. Compared with mice in the AD group, those in the AD+LPS group had further increases in serum inflammatory factors and Aβ levels in the brain ( P<0. 05) and increased coexpression of Flotillin-1 and Aβ1- 42/ APP / BACE1 double-labeled proteins in their cortical brain tissue ( P<0. 05 ) .Compared with mice in the AD+LPS group, those in the AD+LPS+FA group had lower in vivo inflammation levels and Aβcontent in the brain ( P<0. 05) , lower brain tissue Flotillin-1 protein expression ( P<0. 05) , and lower Flotillin-1 and Aβ1- 42 / APP / PS1 / BACE1 protein co-expression in cortical brain tissue ( P<0. 05 ) . Conclusions Folic acid supplementation may reduce Flotillin-1 protein expression and Aβ deposition in the brain of AD inflammatory mice.

Abstract: Objective To explore the hearing and cochlear histomorphological changes in APP / PS1 transgenic mice during the process of AD and to determine whether the occurrence and development of AD affect their hearing function. Methods APP / PS1 transgenic mice and wild type littermates were selected at the ages of 4, 8 and 12 months.Changes to the auditory function of APP / PS1 transgenic mice over time were detected by immunofluorescence staining and auditory brainstem response (ABR) test. Results Compared with the control group, the 4-month-old APP / PS1 transgenic mice had a significantly increased number of Aβ plaques in the hippocampus, indicating that AD symptoms were already present at this time. At the ages of 4, 8 and 12 months, there was no significant difference in the hearing threshold between APP / PS1 transgenic mice and wild type mice. Histomorphological examination of the cochlea showed no significant difference in key cells of the inner ear, such as cochlear hair cells and spiral ganglion, between the two groups of mice. An ABR test showed that the hearing threshold of both APP / PS1 transgenic mice and wild type littermates increased significantly with age, and both groups showed age-related hearing loss. Conclusions There was age-related hearing loss in APP / PS1 transgenic mice, but the occurrence and development of AD had little effect on their auditory functions.

Abstract:Alzheimer’s disease (AD) is a degenerative neurological disorder that can lead to cognitive decline, mental behavior abnormalities, and a reduced ability to undertake daily life activities. Tryptophan is an essential amino acid for the human body and is produced by three main metabolic pathways, namely kynurenine, 5-hydroxytryptamine, and indole derivatives. Influencing the metabolites of tryptophan can ameliorate neuroinflammation in the brain and significantly improve cognitive ability, while the occurrence and development of AD are reduced. In this paper, we review the research literature on the use of tryptophan metabolism intervention in AD in the last 3 years from CNKI, PubMed, and other databases, and summarize its mechanism of action, with a view to providing a reference for further research on anti-AD drugs.

Abstract:The incidence of neurodegenerative diseases (NDs) has been increasing. Current drugs targeting NDs are mainly based on relieving symptoms rather than effecting a cure, and fail to prevent disease progression. Exosomes are a subset of extracellular vesicles that can be produced by almost all cells in the human body and exert biological effects in a variety of ways after their release into the extracellular environment. Many studies have shown that the unique biological characteristics of exosomes mean that they can be used as a tool for the prevention, remission, treatment and diagnosis of NDs. This article reviews the biogenesis of exosomes and their roles in ND, to provide new ideas for the clinical treatment of these conditions.

Abstract:Mitochondria-associated membranes ( MAMs ) are a subcellular compartment involved in the communication and material exchange between the mitochondrial outer membrane and endoplasmic reticulum membrane.MAMs perform various biological processes in cells under different conditions. MAM-dysfunction-mediated calcium homeostasis imbalance, endoplasmic reticulum stress, mitophagy defects, mitochondrial fission / fusion dynamics imbalance, lipid metabolism disorders, and inflammatory responses are key pathogenic factors in Alzheimer’ s disease (AD). This article reviews the structure and function of MAMs, their involvement in AD pathology, and drug intervention targets, and discusses the role of MAMs in the pathogenesis of AD and the latest research into their mechanisms, to provide new ideas for the prevention and treatment of AD.

Abstract:Alzheimer’ s disease ( AD) is a neurodegenerative disorder characterized by widespread dementia.Despite the extensive research conducted on the pathogenesis of AD over the past 50 years, the underlying mechanisms responsible for AD-related cellular damage and cognitive impairment remain elusive. Multiple studies have confirmed alterations in the glucose metabolism patterns occur within the nerve cells of individuals with AD. This metabolic transitionplays a crucial role in cell survival and disease progression, occurring decades before pathological changes and cognitive dysfunction even manifest. This article provides an overview of the potential mechanisms through which glucose metabolism reprogramming contributes to AD development in various types of nerve cells and brain regions, as well as the implication of their interplay. We aim to establish a foundation for further investigations into AD while offering insights and ideas for the development of novel preventive and therapeutic approaches.

Abstract:Microglia efferocytosis, the process by which microglia phagocytose damaged and dead cells, has anti inflammatory and pro-damage repair effects. Recent studies have shown that microglia efferocytosis plays a crucial role in the pathogenesis of Alzheimer’s disease (AD) and may be a novel therapeutic target for AD. This paper reviews the relationship between microglia efferocytosis and AD pathogenesis and the potential of using efferocytosis-related molecules as therapeutic targets for AD. The aim of this review is to provide new ideas and approaches for the treatment of AD.

Abstract: Objective　To investigate the effects of Bushen Jianpi Kaixin formula (BSJPKXF) on the learning and memory abilities of Alzheimer’s disease (AD) model rats, the related autophagy and apoptosis in their cortex, and the underlying mechanism of BSJPKXF. Methods　Sixty rats were randomly divided into six groups (n=10): control group, AD group, Bushen group (BS, 3. 6 g/ (kg·d)), Jianpi group (JP, 4. 05 g/ (kg·d)), Kaixin group (KX, 2. 34 g/ (kg·d)), and Bushen Jianpi Kaixin group (BSJPKXF, 9. 99 g/ (kg·d)). The AD model was established by intraperitoneal injection of D-gal. Rats in BS, JP, KX and BSJPKXF groups were gavaged with corresponding drugs once a day. Rats in control and AD groups were treated with an equal volume of normal saline once per day. After 4 weeks, learning and memory abilities were assessed by the Morris water maze. The open-field test was used to assess cognitive functions. LC3-I, LC3-II and Beclin1 expression in cerebral cortical tissues was detected by Western blot. Bax and Bcl-2 expression in cerebral cortical tissues was detected by immunohistochemistry. Beclin1, P62, Bax and Bcl-2 mRNA expression in cerebral cortical tissues was detected by RT-PCR. Results　Compared with the control group, D-gal significantly decreased the spatial learning and memory abilities in the AD group (P<0. 01), decreased Beclin1, LC3-I/ LC3-II and Bcl-2 expression and the Bcl-2/ Bax ratio, and increased P62 and Bax mRNA expression (P<0. 01). After treatment, compared with the AD model group, Bushen Jianpi Kaixin formula improved the spatial learning memory ability in the BSJPKXF group (P<0. 01), increased Beclin1, LC3-I/ LC3-II and Bcl-2 expression and the Bcl-2/ Bax ratio, and decreased P62 and Bax mRNA expression (P<0. 01). Conclusions　Bushen Jianpi Kaixin formula improved cognitive impairment in AD rats. The mechanism was presumed related to the reduction of neural autophagy and apoptosis.

Abstract:Alzheimer’s disease (AD) is an irreversible heterogeneous neurodegenerative disease. AD patients have memory loss and impaired synaptic plasticity. In view of cAMP responsive element-binding protein (CREB), which is intimately associated with synaptic plasticity, this article summarizes the research progress on the structure, signaling pathways, downstream genes, and relative memory regulation. The involvement of CREB in AD development serves as a reference for AD researchers to improve synaptic plasticity.