Clinical evidence of human pathogens implicated in Alzheimer ’s disease pathology and the therapeutic efficacy of antimicrobials: an overview
AbstractA wealth of pre-clinical reports and data derived from human subjects and brain autopsies suggest that microbial infections are relevant to Alzheimer ’s disease (AD). This has inspired the hypothesis that microbial infections increase the risk or even trigger the onset of AD. Multiple models have been developed to explain the increase in pathogenic microbes in AD patients. Although this hypothesis is well accepted in the field, it is not yet cl ear whether microbial neuroinvasion is a cause of AD or a consequence of the pathological changes experienced by the demented brain. Along the same line, the gut microbiom...
Source: Translational Neurodegeneration - July 26, 2023 Category: Neurology Source Type: research
Animal models of Parkinson ’s disease: bridging the gap between disease hallmarks and research questions
AbstractParkinson ’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical description, PD remains a serious affliction that affects a growing proportion of the population. Prevailing treatments only alleviate symptoms; t here is still neither a cure that targets the neurodegenerative processes nor therapies that modify the course of the disease. Over the past decades, several animal models have been developed to study PD. Although no model precisely recapitulates the pathology, they still provide valuable informatio n that con...
Source: Translational Neurodegeneration - July 19, 2023 Category: Neurology Source Type: research
Impact of seed amplification assay and surface-enhanced Raman spectroscopy combined approach on the clinical diagnosis of Alzheimer ’s disease
ConclusionsSuch analytical approach can be used to recognize disease features, thus allowing early stratification and selection of patients, which is fundamental in clinical treatments and pharmacological trials. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - July 12, 2023 Category: Neurology Source Type: research
Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints
ConclusionPlasma p-tau181, as well as18F-florbetapir and18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of A β status in symptomatic stages of AD.18F-Florzolotau and18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment. Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - June 29, 2023 Category: Neurology Source Type: research
Brain metabolism in Alzheimer ’s disease: biological mechanisms of exercise
AbstractAlzheimer ’s disease (AD) is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation of multiple adverse factors, accompanied by dysregulation of numerous intracellular signaling and molecular pathways in the brain. At the cellular and molecular levels, the neuronal c ellular milieu of the AD brain exhibits metabolic abnormalities, compromised bioenergetics, impaired lipid metabolism, and reduced overall metabolic capacity, which lead to abnormal neural network activity and impaired neuroplasticity, thus accelerating the formation of extracellular senile plaques and intrace...
Source: Translational Neurodegeneration - June 26, 2023 Category: Neurology Source Type: research
Update on the pathological roles of prostaglandin E2 in neurodegeneration in amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons. The pathogenesis of ALS remains largely unknown; however, inflammation of the spinal cord is a focus of ALS research and an important pathogenic process in ALS. Prostaglandin E2 (PGE2) is a major lipid mediator generated by the arachidonic-acid cascade and is abundant at inflammatory sites. PGE2 levels are increased in the postmortem spinal cords of ALS patients and in ALS model mice. Beneficial therapeutic effects have been obtained in ALS model mice using cycloox...
Source: Translational Neurodegeneration - June 19, 2023 Category: Neurology Source Type: research
Reciprocal effects of alpha-synuclein aggregation and lysosomal homeostasis in synucleinopathy models
ConclusionsOur findings demonstrate a strong interplay between αSyn aggregation pathways and function of lysosomal cathepsins. It appears that αSyn directly interferes with the enzymatic function of cathepsins, which might lead to a vicious cycle of impaired αSyn degradation.Graphical abstractLysosomal trafficking of cathepsin D (CTSD), CTSL and CTSB is disrupted when alpha-synuclein ( αSyn) is aggregated. This results in a decreased proteolytic activity of cathepsins, which directly mediate αSyn clearance. Boosting the transport of the cathepsins to the lysosome increases their activity and thus contributes to effici...
Source: Translational Neurodegeneration - June 13, 2023 Category: Neurology Source Type: research
Defective lysosomal acidification: a new prognostic marker and therapeutic target for neurodegenerative diseases
AbstractLysosomal acidification dysfunction has been implicated as a key driving factor in the pathogenesis of neurodegenerative diseases, including Alzheimer ’s disease and Parkinson’s disease. Multiple genetic factors have been linked to lysosomal de-acidification through impairing the vacuolar-type ATPase and ion channels on the organelle membrane. Similar lysosomal abnormalities are also present in sporadic forms of neurodegeneration, although the underlying pathogenic mechanisms are unclear and remain to be investigated. Importantly, recent studies have revealed early occurrence of lysosomal acidification impairme...
Source: Translational Neurodegeneration - June 8, 2023 Category: Neurology Source Type: research
Cognitive dysfunction of patients infected with SARS-CoV-2 omicron variant in Shanghai, China
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 24, 2023 Category: Neurology Source Type: research
Longitudinal evolution of cortical thickness signature reflecting Lewy body dementia in isolated REM sleep behavior disorder: a prospective cohort study
ConclusionCortical thickness signature can effectively reflect the longitudinal evolution of Lewy body dementia in the iRBD population. Replication studies would further validate the utility of this imaging marker in iRBD. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 22, 2023 Category: Neurology Source Type: research
An open-label multiyear study of sargramostim-treated Parkinson ’s disease patients examining drug safety, tolerability, and immune biomarkers from limited case numbers
ConclusionsTaken together, the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment. Confirmation in larger patient populations is planned in a future phase II evaluation.Trial registration: ClinicalTrials.gov: NCT03790670, Date of Registration: 01/02/2019, URL:https://clinicaltrials.gov/ct2/show/NCT03790670?cond=leukine+parkinson%27s&draw=2&rank=2. (Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 22, 2023 Category: Neurology Source Type: research
Perivascular spaces relate to the course and cognition of Huntington ’s disease
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 15, 2023 Category: Neurology Source Type: research
Early life adversity as a risk factor for cognitive impairment and Alzheimer ’s disease
AbstractNeurological conditions, including cognitive impairment and Alzheimer ’s disease (AD), impose a huge burden on society, affecting millions of people globally. In addition to genetic factors, recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases. Early life adversity (ELA) has a profound impact on bra in function and health later in life. In rodent models, exposure to ELA results in specific cognitive deficits and aggravated AD pathology. Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people wit...
Source: Translational Neurodegeneration - May 12, 2023 Category: Neurology Source Type: research
A phase 1b randomized clinical trial of CT1812 to measure A β oligomer displacement in Alzheimer’s disease using an indwelling CSF catheter
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 12, 2023 Category: Neurology Source Type: research
Correction: Links between COVID-19 and Parkinson ’s disease/Alzheimer’s disease: reciprocal impacts, medical care strategies and underlying mechanisms
(Source: Translational Neurodegeneration)
Source: Translational Neurodegeneration - May 12, 2023 Category: Neurology Source Type: research
