AI Article Synopsis
Article Abstract
Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death. The blood-cerebrospinal fluid (CSF) barrier consists of a monolayer of choroid plexus epithelial (CPE) cells, and AD is associated with changes in CPE cell morphology. Here, we report that TNF is the main inflammatory upstream mediator in choroid plexus tissue in AD patients. This was confirmed in two murine AD models: transgenic APP/PS1 mice and intracerebroventricular (icv) AβO injection. TNFR1 contributes to the morphological damage of CPE cells in AD, and TNFR1 abrogation reduces brain inflammation and prevents blood-CSF barrier impairment. In APP/PS1 transgenic mice, TNFR1 deficiency ameliorated amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR1 rescued from the induced cognitive impairments. Our data indicate that TNFR1 is a promising therapeutic target for AD treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887909 | PMC |
| http://dx.doi.org/10.15252/emmm.201708300 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The CareVirtue Digital Journal for Family and Friend Caregivers of People Living With Alzheimer Disease and Related Dementias: Exploratory Topic Modeling and User Engagement Study.
JMIR Aging
December 2024
Department of Health & Wellness Design, School of Public Health- Bloomington, Indiana University, Bloomington, IN, United States.
Background: As Alzheimer disease (AD) and AD-related dementias (ADRD) progress, individuals increasingly require assistance from unpaid, informal caregivers to support them in activities of daily living. These caregivers may experience high levels of financial, mental, and physical strain associated with providing care. CareVirtue is a web-based tool created to connect and support multiple individuals across a care network to coordinate care activities and share important information, thereby reducing care burden.
View Article and Find Full Text PDFSynaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's disease (PD), occurring before widespread protein aggregation, neuronal loss, and cognitive decline. While the field has focused on the aggregation of Tau and α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even before their aggregation. Therefore, understanding the mechanisms by which Tau and α-Syn affect presynaptic terminals offers an opportunity for developing innovative therapeutics aimed at preserving synapses and potentially halting neurodegeneration.
View Article and Find Full Text PDFUltrasensitive Protein Aggregate Quantification Assays for Neurodegenerative Diseases on the Simoa Platform.
Anal Chem
December 2024
Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
Nanoscale aggregates play a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. However, quantifying these aggregates in complex biological samples, such as biofluids and postmortem brain tissue, has been challenging due to their low concentration and small size, necessitating the development of methods with high sensitivity and specificity. Here, we have developed ultrasensitive assays utilizing the Quanterix Simoa platform to detect α-synuclein, β-amyloid and tau aggregates, including those with common posttranslational modifications such as truncation of α-synuclein and AT8 phosphorylation of tau aggregates.
View Article and Find Full Text PDFPrecision diagnosis of cognitive impairment due to Alzheimer's disease for therapeutic interventions.
Alzheimers Dement
December 2024
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
With the advent of anti-amyloid monoclonal antibody (AAMA) therapy, precision diagnosis is necessary for identifying appropriate patients with cognitive disorders due to Alzheimer's disease. Therapy with AAMAs requires that candidates be diagnosed with mild cognitive impairment or mild dementia, have elevated brain amyloid-β, have good physical, psychiatric, and medical health, and lack clinical or biomarker evidence of potentially impactful non-Alzheimer brain disorders. The first three diagnostic activities are the core of the Clinical Practice Guidelines, but the last element of the precision diagnosis requires new decision-making tools for recognizing multi-etiology cognitive impairment.
View Article and Find Full Text PDFNext generation brain health: transforming global research and public health to promote prevention of dementia and reduce its risk in young adult populations.
Lancet Healthy Longev
December 2024
Global Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland; Centre for Dementia Research, School of Health, Leeds Beckett University, Leeds, UK.
Efforts to prevent dementia can benefit from precision interventions delivered to the right population at the right time; that is, when the potential to reduce risk is the highest. Young adults (aged 18-39 years) are a neglected population in dementia research and policy making despite being highly exposed to several known modifiable risk factors. The risk and protective factors that have the biggest effect on dementia outcomes in young adulthood, and how these associations differ across regions and groups, still remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!