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BACKGROUND: Sarcopenia, the age-related loss of muscle mass and function, brings multiple adverse outcomes including disability and death. Several sarcopenia consensuses have newly introduced the premorbid concept of possible sarcopenia and recommended early lifestyle interventions. Bidirectional transitions of premorbid states have been revealed in several chronic diseases yet not clarified in sarcopenia. This study aims to investigate the underlying transition patterns of sarcopenia states. METHODS: The study utilized three waves of data from a nationally representative survey, the China Health and Retirement Longitudinal Study (CHARLS), and included community-dwelling individuals aged 60 years and older with at least two sarcopenia states assessments based on the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019) between 2011 and 2015. The estimated transition intensity and probability between non-sarcopenia, possible sarcopenia, sarcopenia, and death were investigated using multi-stage Markov (MSM) models. RESULTS: The study comprised 4395 individuals (49.2% female, median age 67 years) with a total of 10 778 records of sarcopenia state assessment, and the mean follow-up period was 3.29 years. A total of 24.5% of individuals with a current state of possible sarcopenia returned to non-sarcopenia, 60.3% remained possible sarcopenia, 6.7% progressed to sarcopenia, and 8.5% died by the next follow-up. The transition intensity of recovery to non-sarcopenia (0.252, 95% CI 0.231-0.275) was 2.8 times greater than the deterioration to sarcopenia (0.090, 95% CI 0.080-0.100) for individuals with possible sarcopenia. For individuals with possible sarcopenia, the estimated probabilities of recovering to non-sarcopenia, progressing to sarcopenia, and transitioning to death within a 1-year observation were 0.181, 0.066, and 0.035, respectively. For individuals with sarcopenia, the estimated probabilities of recovering to non-sarcopenia, recovering to possible sarcopenia, and transitioning to death within 1-year observation were 0.016, 0.125, and 0.075, respectively. In covariables analysis, age, sex, body mass index, physical function impairment, smoking, hypertension, and diabetes are important factors influencing bidirectional transitions. CONCLUSIONS: The findings highlight the bidirectional transitions of sarcopenia states among older adults and reveal a notable proportion of possible sarcopenia show potential for recovery in the natural course. Screening and intensifying interventions based on risk factors may facilitate a recovery transition.
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BACKGROUND: The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. METHODS: This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. RESULTS: Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36-2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82-0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32-2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51-5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. CONCLUSION: We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population.
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Vacunas contra la COVID-19 , COVID-19 , Accidente Cerebrovascular , Vacilación a la Vacunación , Humanos , Masculino , Femenino , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Persona de Mediana Edad , Estudios Transversales , Anciano , COVID-19/prevención & control , COVID-19/psicología , Vacilación a la Vacunación/psicología , Vacilación a la Vacunación/estadística & datos numéricos , Accidente Cerebrovascular/psicología , China , Factores de Riesgo , SARS-CoV-2RESUMEN
Trillions of intestinal bacteria in the human body undergo dynamic transformations in response to physiological and pathological changes. Alterations in their composition and metabolites collectively contribute to the progression of Alzheimer's disease. The role of gut microbiota in Alzheimer's disease is diverse and complex, evidence suggests lipid metabolism may be one of the potential pathways. However, the mechanisms that gut microbiota mediate lipid metabolism in Alzheimer's disease pathology remain unclear, necessitating further investigation for clarification. This review highlights the current understanding of how gut microbiota disrupts lipid metabolism and discusses the implications of these discoveries in guiding strategies for the prevention or treatment of Alzheimer's disease based on existing data.
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Enfermedad de Alzheimer , Microbioma Gastrointestinal , Humanos , Enfermedad de Alzheimer/metabolismo , Microbioma Gastrointestinal/fisiología , Metabolismo de los Lípidos , Progresión de la Enfermedad , LípidosRESUMEN
Exercise elicits a wide range of physiological responses in mammalian tissues that enhance a broad range of functions, particularly in improving cognitive performance. However, the field lacks a comprehensive bibliometric analysis that clarifies its knowledge structure and research hotspots. This study aims to address this gap and map the research landscape regarding the role of exercise in cognitive function enhancement. Firstly, the frequencies and co-occurrence of keywords were analysed to identify six main clusters: aging, cognitive impairment, rehabilitation, obesity, fatigue, and hippocampus. Secondly, reference timeline co-citation analysis revealed that hippocampus and aging were the major bursts with high intensity and long attention span while children had recently emerged as a topical subject. Finally, the evolution of themes from 2012 to 2022 was analysed, and found that older adults had been the leading research theme for exercise affecting cognition. Childhood obesity was an emerging theme that attracted increasing research attention in recent years while the hippocampus research theme expanded rapidly during the decade but remained a niche topic with less relevance to others. This research identified and summarised research priorities and evolutionary trends in exercise to improve cognition by constructing knowledge networks through visual analysis. It provides researchers with a comprehensive insight into the current state of the field to facilitate further research.
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Disfunción Cognitiva , Obesidad Infantil , Niño , Animales , Humanos , Anciano , Cognición , Envejecimiento , Ejercicio Físico , MamíferosRESUMEN
Background and objectives: Global aging has increased the importance of health management in older adults. Exercise is a crucial strategy for healthy aging and has led to numerous scientific advancements due to its impact on age-related illnesses. We aim to investigate the research hotspots, bursts of knowledge base, and trends in the field of exercise and physical activity in older adults over the past decade and present them in a visual manner. Methods: We searched and retrieved data from the Web of Science database, and performed a bibliometric analysis of publications on exercise and physical activity research in older adults from 2013 to 2022. We evaluated the current status and hotspots through co-occurrence analysis using VOSviewer. The evolution and bursts of knowledge base were assessed through co-citation analysis using CiteSpace. Thematic evolution was analyzed using the bibliometrix package to discover keyword trends. The attribution and collaboration of countries/regions, institutions and authors were also analyzed. Results: A total of 27,820 publications were included. Publications on exercise and physical activity in older adults increased from 1755 records in 2013-3737 records in 2022 annually. In co-occurrence analysis of keywords, 5 major clusters were revealed: sarcopenia, cognition, frailty, mental health, and rehabilitation. Co-citation analysis reveals that the knowledge base has evolved from references focused on frailty, dementia, and physical activity before 2016 to references focus on sarcopenia, cognition and sedentary behavior after 2020. Among the top 10 high-frequency keywords, sarcopenia demonstrated a consistent and significant upward trend, with its percentage increasing from 8.7 % (82 times) in 2016 to 12.2 % (236 times) in the most recent year, making it the most frequently used keyword. Frailty ranked second, starting at 5.6 % (41 times) in 2013 and gradually rising to 11.7 % (225 times) in 2022. The most productive country, institution and author were the USA (8212 publications), the University of Pittsburgh(501 publications), and Brendon Stubbs(94 publications), respectively. Discussion: Publications on exercise and physical activity for older adults have surged in the last decade, accompanied by a shift in the knowledge base. Regional disparities in the academic output in this field need to be addressed in the future to promote healthy aging.
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Background: As the primary caregivers for people with dementia in China, family caregivers face a significant care burden that can negatively impact their mental and physical health. It is vital to investigate ways to support these caregivers. Objective: To assess the effectiveness of a program led by community nurses to support caregivers of individuals with dementia. Methods: A total of 30 caregivers received nurse-led support in addition to usual care, while 28 caregivers received only usual care. The primary outcome was caregivers' sense of competency in providing dementia care, which was measured using the Short Sense of Competence Questionnaire (SSCQ). Secondary outcomes included caregivers' ability to perform daily activities, behavioral and psychological symptoms of dementia (BPSD) using a neuropsychiatric inventory questionnaire, and quality of life using the short form health survey (SF-36). The trial was registered at the Chinese Clinical Trial Registry (ChiCTR 2300071484). Results: Compared to the control group, the intervention group had significantly higher SSCQ scores and a lower caregiver distress index over time. Physical and mental health-related quality of life also improved significantly among caregivers in the intervention group. However, there was no significant difference between the two groups in terms of activities of daily living and BPSD. Conclusions: The community nurse-led support program significantly improved caregivers' competency in providing dementia care and quality of life and reduced distress. These findings have important implications for dementia care policies, resources, and workforce development in China, including strengthening community dementia care services through collaboration with specialists in hospitals.
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Helicobacter pylori (H. pylori) infection confers risk for Alzheimer's Disease (AD), with the mechanisms unknown. Infections are linked to the etiology of AD partly through modulating the humoral immunity post-infection. This study found increased plasma levels of tTau and pTau181 in H. Pylori infected individuals with intact cognition. Plasma antibodies to H. pylori were positively associated with Aß40, Aß42, tTau, and pTau181, adjusting for age, sex, education level, BMI, ApoE ε4 genotype, hypertension, diabetes mellitus, and hypercholesteremia. This study presents novel insights into the relationship between H. pylori infection and AD from an autoimmune perspective.
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Enfermedad de Alzheimer , Diabetes Mellitus , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Adulto , Biomarcadores , Infecciones por Helicobacter/complicacionesRESUMEN
Amyloid ß (Aß) and tau play pivotal roles in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that brain-derived Aß and tau can be cleared through transport into the periphery, and the kidneys may be vital organs involved in the clearance of Aß and tau. However, the effects of deficiency in the clearance of Aß and tau by the kidneys on brain AD-type pathologies in humans remain largely unknown. In this study, we first recruited 41 patients with chronic kidney disease (CKD) and 40 age- and sex-matched controls with normal renal function to analyze the associations of the estimated glomerular filtration rate (eGFR) with plasma Aß and tau levels. To analyze the associations of eGFR with cerebrospinal fluid (CSF) AD biomarkers, we recruited 42 cognitively normal CKD patients and 150 cognitively normal controls with CSF samples. Compared with controls with normal renal function, CKD patients had higher plasma levels of Aß40, Aß42 and total tau (T-tau), lower CSF levels of Aß40 and Aß42 and higher levels of CSF T-tau/Aß42 and phosphorylated tau (P-tau)/Aß42. Plasma Aß40, Aß42, and T-tau levels were negatively correlated with eGFR. In addition, eGFR was negatively correlated with CSF levels of T-tau, T-tau/Aß42, and P-tau/Aß42 but positively correlated with Mini-Mental State Examination (MMSE) scores. Thus, this study showed that the decline in renal function was correlated with abnormal AD biomarkers and cognitive decline, which provides human evidence that renal function may be involved in the pathogenesis of AD.
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Enfermedad de Alzheimer , Insuficiencia Renal Crónica , Humanos , Péptidos beta-Amiloides , Enfermedad de Alzheimer/patología , Proteínas tau/líquido cefalorraquídeo , Biomarcadores , Fragmentos de Péptidos , Riñón/fisiología , Riñón/patologíaRESUMEN
Acetone-butanol-ethanol (ABE) fermentation is a traditional way for solvents production through bioconversion by Clostridium species. It is still a challenge to obtain metabolic engineering strains with high ABE yield. Screening strains with remarkable characteristics from nature and improving ABE yield by mutation are viable approaches. Clostridium beijerinckii XH 0906, a newly isolated strain, produces butanol and isopropanol (BI) as the main end-products (9.1 g/L BI) during fermentation with glucose as the sole carbon source. The screening process for this strain was performed under aerobic conditions rather than anaerobic environment. Thus, it is a robust stain capable of oxygen-tolerant BI fermentation. Furthermore, C. beijerinckii XH 0906 fermented xylose and glucose simultaneously to produce BI. A mutant strain obtained by ultraviolet (UV) mutagenesis, C. beijerinckii XH 29, had improved BI production capacity and could produce 17.0 g/L BI and 18.4 g/L BI using glucose or corn stover hydrolysate, respectively as the carbon source. Interestingly, C. beijerinckii XH 29 also produced up to 19.3 g/L isopropanol through fermentation of a glucose-acetone mix. These results indicate that C. beijerinckii XH 29 is an excellent BI producer with great potential for industrial applications.
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Increased neuronal apoptosis is an important pathological feature of Alzheimer's disease (AD). The Bcl-2-interacting mediator of cell death (Bim) mediates amyloid-beta (Aß)-induced neuronal apoptosis. Naturally-occurring antibodies against Bim (NAbs-Bim) exist in human blood, with their levels and functions unknown in AD. In this study, we found that circulating NAbs-Bim were decreased in AD patients. Plasma levels of NAbs-Bim were negatively associated with brain amyloid burden and positively associated with cognitive functions. Furthermore, NAbs-Bim purified from intravenous immunoglobulin rescued the behavioral deficits and ameliorated Aß deposition, tau hyperphosphorylation, microgliosis, and neuronal apoptosis in APP/PS1 mice. In vitro investigations demonstrated that NAbs-Bim were neuroprotective against AD through neutralizing Bim-directed neuronal apoptosis and the amyloidogenic processing of amyloid precursor protein. These findings indicate that the decrease of NAbs-Bim might contribute to the pathogenesis of AD and immunotherapies targeting Bim hold promise for the treatment of AD.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones TransgénicosRESUMEN
Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.
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Péptidos beta-Amiloides/toxicidad , Receptores de Factor de Crecimiento Nervioso/metabolismo , Tauopatías/metabolismo , Proteínas tau/metabolismo , Animales , Células Cultivadas , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Distribución Aleatoria , Receptores de Factor de Crecimiento Nervioso/administración & dosificación , Receptores de Factor de Crecimiento Nervioso/genética , Tauopatías/tratamiento farmacológico , Tauopatías/genética , Proteínas tau/antagonistas & inhibidores , Proteínas tau/genéticaRESUMEN
Emerging evidence suggests that gut microbiota dysbiosis plays a role in neurodegenerative disorders. However, whether the composition and diversity of the gut microbiota are altered in tauopathies remains largely unknown. This study was aimed to examine the diversity and composition of the gut microbiota in tauopathies, as well as the correlation with pathological changes in the brain. We collected fecal samples from 32 P301L tau transgenic mice and 32 age- and gender-matched littermate mice at different ages. The 16S ribosomal RNA sequencing technique was used to analyze the microbiota composition in feces. Brain tau pathology levels were measured by immunohistochemistry. The diversity and composition of the gut microbiota significantly changed with aging. At the phylum level, the relative abundance of Bacteroidetes was increased, while Firmicutes were decreased in P301L mice compared with that in Wt mice after 3 months of age. In addition, Actinobacteria was decreased in P301L mice at 3 and 6 months of age, meanwhile Tenericutes was decreased in P301L mice at 10 months of age. Moreover, several specific macrobiota were highly associated with the levels of AT8-tau or pT231-tau protein in the brain. Our findings suggest that gut microbiota changed with aging, as well as in the tauopathy mice model. Modulation of the gut microbiota may be a potential strategy for treatment of tauopathy.
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Modelos Animales de Enfermedad , Microbioma Gastrointestinal/genética , Tauopatías/genética , Tauopatías/microbiología , Animales , Humanos , Ratones , Ratones Transgénicos , Factores de TiempoRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disease characterized by neuronal loss in the substantia nigra. The p75 neurotrophin receptor (p75NTR, encoded by NGFR) was found to play an important role in the selective neuronal death of dopamine neurons in the substantia nigra, as well as the pathogenesis and development of PD. To assess the association between NGFR gene polymorphism and the susceptibility of PD, this case-control study consisting of 414 PD patients and 623 age- and sex-matched controls in a Chinese Han cohort was conducted. Twelve tag-single nucleotide polymorphisms (tag-SNPs) were selected from the NGFR gene through the construction of linkage disequilibrium blocks. One tag-SNP from the ADAM17 gene was also selected owing to its function of encoding tumor necrosis factor α-converting enzyme, which is responsible for the shedding of the extracellular domain of p75NTR. A multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) method was applied for genotyping. The associations between tag-SNPs and the risk of PD with the adjustment for age and sex were analyzed by unconditional logistic regression, and five genetic models including codominant, dominant, recessive, over-dominant, and additive models were applied. The results showed that among the 13 tag-SNPs, rs741073 was associated with a reduced risk of PD in the codominant (OR = 0.71, 95% CI = 0.54-0.93, P = 0.037), dominant (OR = 0.76, 95% CI = 0.58-0.98, P = 0.033), and over-dominant models (OR = 0.71, 95% CI = 0.54-0.92, P = 0.010), and rs1804011 was also associated with a reduced risk of PD in the codominant (OR = 0.69, 95% CI = 0.50-0.95, P = 0.049), dominant (OR = 0.69, 95% CI = 0.50-0.93, P = 0.014), over-dominant (OR = 0.70, 95% CI = 0.51-0.96, P = 0.025), and additive models (OR = 0.72, 95% CI = 0.54-0.94, P = 0.016). However, these associations did not retain after Bonferroni correction. Conclusively, our study failed to reveal the association between the selected tag-SNPs within NGFR, ADAM17, and the susceptibility of PD. The role of p75NTR and its gene polymorphisms in the pathogenesis of PD needs to be further studied.
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Proteína ADAM17/genética , Pueblo Asiatico/genética , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Factor de Crecimiento Nervioso/genética , Anciano , Estudios de Casos y Controles , China , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Humanos , MasculinoRESUMEN
Brain amyloid-ß (Aß) deposition is a hallmark to define Alzheimer's disease (AD). We investigated the positive rate of brain amyloid deposition assessed with 11C-Pittsburgh compound (PiB)-PET and blood Aß levels in a cohort of probable AD patients who were diagnosed according to the 1984 NINCDS-ADRDA criteria. Eighty-four subjects with a clinical diagnosis of probable AD dementia, amnestic mild cognitive impairment (MCI), and cognitively normal (CN) status were subjected to PiB-PET and 18F-fluorodeoxyglucose (FDG)-PET scans. Plasma biomarkers of Aß42, Aß40, and T-tau were measured using single molecule array technology. The positive rate of PiB-PET, the associations between PiB-PET status and FDG-PET, plasma biomarkers, and clinical manifestations were analyzed. PiB-PET was positive in 77.36% of probable AD patients, 31.80% of MCI patients, and 0 of NC. Plasma Aß42/Aß40 ratio was associated with PiB-PET, the ROC curve analysis revealing an AUC of 0.77 (95% CI: 0.66-0.87), with a sensitivity of 82% and specificity of 64%. Some clinical manifestations were associated with PiB-PET imaging. Our findings indicate that only three-fourths of patients diagnosed with probable AD fit the pathological criteria, suggesting that we should be cautious regarding the accuracy of AD diagnosis when no biomarker evidence is available in our clinical practice.
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Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Fragmentos de Péptidos/metabolismo , Proteínas tau/metabolismo , Anciano , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/sangre , Biomarcadores/sangre , Encéfalo/patología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/patología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Tomografía de Emisión de Positrones , Proteínas tau/sangreRESUMEN
Accumulation of pathological tau is the hallmark of Alzheimer's disease and other tauopathies and is closely correlated with cognitive decline. Clearance of pathological tau from the brain is a major therapeutic strategy for tauopathies. The physiological capacity of the periphery to clear brain-derived tau and its therapeutic potential remain largely unknown. Here, we found that cisterna magna injected 131I-labelled synthetic tau dynamically effluxed from the brain and was mainly cleared from the kidney, blood, and liver in mice; we also found that plasma tau levels in inferior vena cava were lower than those in femoral artery in humans. These findings suggest that tau proteins can efflux out of the brain and be cleared in the periphery under physiological conditions. Next, we showed that lowering blood tau levels via peritoneal dialysis could reduce interstitial fluid (ISF) tau levels in the brain, and tau levels in the blood and ISF were dynamically correlated; furthermore, tau efflux from the brain was accelerated after the addition of another set of peripheral system in a parabiosis model. Finally, we established parabiosis mouse models using tau transgenic mice and their wild-type littermates and found that brain tau levels and related pathologies in parabiotic transgenic mice were significantly reduced after parabiosis, suggesting that chronic enhancement of peripheral tau clearance alleviates pathological tau accumulation and neurodegeneration in the brain. Our study provides the first evidence of physiological clearance of brain-derived pathological tau in the periphery, suggesting that enhancing peripheral tau clearance is a potential therapeutic strategy for tauopathies.
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Sistema Nervioso Periférico/metabolismo , Tauopatías/metabolismo , Tauopatías/terapia , Proteínas tau/metabolismo , Adulto , Anciano , Animales , Química Encefálica , Cisterna Magna/metabolismo , Líquido Extracelular/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Parabiosis , Diálisis Peritoneal , Distribución Tisular , Vena Cava Inferior/metabolismo , Proteínas tau/genéticaRESUMEN
Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aß), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
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Enfermedad de Alzheimer , Investigación Biomédica/métodos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/terapia , Animales , Biomarcadores/sangre , Progresión de la Enfermedad , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Tau pathology is characterized as a form of frontotemporal lobar degeneration (FTLD) known as FTLD-tau. The underlying pathogenic mechanisms are not known and no therapeutic interventions are currently available. Here, we report that the neurotrophin receptor p75NTR plays a critical role in the pathogenesis of FTLD-tau. The expression of p75NTR and the precursor of nerve growth factor (proNGF) were increased in the brains of FTLD-tau patients and mice (P301L transgenic). ProNGF-induced tau phosphorylation via p75NTR in vitro, which was associated with the AKT/glycogen synthase kinase (GSK)3ß pathway. Genetic reduction of p75NTR in P301L mice rescued the memory deficits, alleviated tau hyperphosphorylation and restored the activity of the AKT/GSK3ß pathway. Treatment of the P301L mice with the soluble p75NTR extracellular domain (p75ECD-Fc), which can antagonize neurotoxic ligands of p75NTR, effectively improved memory behavior and suppressed tau pathology. This suggests that p75NTR plays a crucial role in tau paGSKthology and represents a potential druggable target for FTLD-tau and related tauopathies.
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Degeneración Lobar Frontotemporal/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Precursores de Proteínas/metabolismo , Receptores de Factor de Crecimiento Nervioso/metabolismo , Proteínas tau/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Células Cultivadas , Femenino , Degeneración Lobar Frontotemporal/patología , Degeneración Lobar Frontotemporal/terapia , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Masculino , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Trastornos de la Memoria/terapia , Ratones Transgénicos , Neuronas/metabolismo , Neuronas/patología , Fosforilación/fisiología , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Previous studies have suggested that cardiovascular functions might play a critical role in Alzheimer's disease (AD) pathogenesis. However, the relationship among heart function, blood flow of cerebral vessels, and AD remains unclear. In the present study, AD patients (nâ=â34) and age- and gender-matched cognitively normal controls (nâ=â34) were recruited. Demographic and comorbidity information was collected. The ejection fraction was measured using echocardiography, and the mean velocity, pulsatility index (PI), and resistance index (RI) of the basilar artery (BA), left terminal internal carotid artery (LTICA), and right terminal internal carotid artery (RTICA) were measured using transcranial Doppler. The data of lacunae, white matter changes, and plaques in the aortic arch and carotid arteries were collected from brain magnetic resonance imaging and computed tomography angiography images. Compared with normal controls, AD patients had lower ejection fractions and cerebral blood flow velocities and higher RI and PI in the BA, LTICA, and RTICA, as well as more plaques in the aortic and carotid arteries. In the multivariate logistic regression analysis, the ejection fraction and the mean velocity of the BA and LTICA were independently associated with AD after adjusting for age, gender, education, vascular risk factors, arterial plaques, and brain ischemic lesions detected in the brain images. These findings suggest that heart function and vascular condition may play important roles in AD pathogenesis. Improving cardiovascular functions could be a promising approach for the prevention and treatment of AD.
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Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Sistema Cardiovascular/diagnóstico por imagen , Sistema Cardiovascular/fisiopatología , Anciano , Velocidad del Flujo Sanguíneo , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Circulación Cerebrovascular , Comorbilidad , Electrocardiografía , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Flujo Sanguíneo Regional , Volumen Sistólico , Ultrasonografía Doppler TranscranealRESUMEN
Alzheimer disease (AD) has been made a global priority for its multifactorial pathogenesis and lack of disease-modifying therapies. We sought to investigate the changes of profile of blood routine in AD and its correlation with the disease severity.In all, 92 AD patients and 84 age and sex-matched normal controls were enrolled and their profiles of blood routine were evaluated.Alzheimer disease patients had increased levels of mean corpuscular hemoglobin, mean corpuscular volume, red cell distribution width-standard deviation, mean platelet volume,and decreased levels of platelet distribution width, red blood cell, hematocrit, hemoglobin, lymphocyte, and basophil compared with normal controls.Alterations in quantity and quality of blood cells may be involved in the pathogenesis of AD and contribute to the disease progression.
Asunto(s)
Enfermedad de Alzheimer/sangre , Anciano , Enfermedad de Alzheimer/patología , Biomarcadores/sangre , Estudios de Casos y Controles , Índices de Eritrocitos , Eritrocitos/química , Eritrocitos/patología , Femenino , Ácido Fólico/sangre , Hematócrito , Hemoglobinas/análisis , Humanos , Recuento de Leucocitos , Linfocitos/química , Linfocitos/patología , Masculino , Escala del Estado Mental , Recuento de Plaquetas , Índice de Severidad de la Enfermedad , Vitamina B 12/sangreRESUMEN
BACKGROUND: Nutrition is important for the fetal developmental programming. Nutritional deficiency in early life could increase the susceptibility to many aging-related disorders including cognitive decline. OBJECTIVE: Our study aims to investigate the effect of early famine exposure on aging-associated cognitive function. METHODS: We recruited 6790 subjects born between 1956 to 1964 during which the Great Chinese Famine occurred (1959-1961). Cognitive function of these subjects were evaluated using the Mini-Mental State Examination (MMSE), the Activities of Daily Living scale (ADL), the Instrumental Activities of Daily Living scale (IADL) and the Clinical Dementia Rating (CDR). RESULTS: Our study identified that early exposure to the famine significantly increased the risk of cognitive impairments in later life, leading to higher prevalence of Mild Cognitive Impairment (MCI) and dementia. We also found the sex and rural-urban differences in this malnutrition-induced effect. Illiteracy, history of stroke or diabetes mellitus are great risk factors to facilitate the cognitive decline. CONCLUSION: These findings demonstrate that exposure to famine during early life including prenatal period and early childhood facilitates aging-associated cognitive deficits.