TYROBP/DAP12 forms complexes with ectodomains of immune receptors (TREM2, SIRPβ1, CR3) associated with Alzheimer's disease (AD) and is a network hub and driver in the complement subnetwork identified by multi-scale gene network studies of postmortem human AD brain. Using transgenic or viral approaches, we characterized in mice the effects of TYROBP deficiency on the phenotypic and pathological evolution of tauopathy. Biomarkers usually associated with worsening clinical phenotype (i.e., hyperphosphorylation and increased tauopathy spreading) were unexpectedly increased in MAPT;Tyrobp mice despite the improved learning behavior and synaptic function relative to controls with normal levels of TYROBP. Notably, levels of complement cascade initiator C1q were reduced in MAPT;Tyrobp mice, consistent with the prediction that C1q reduction exerts a neuroprotective effect. These observations suggest a model wherein TYROBP-KO-(knock-out)-associated reduction in C1q is associated with normalized learning behavior and electrophysiological properties in tauopathy model mice despite a paradoxical evolution of biomarker signatures usually associated with neurological decline.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447470PMC
http://dx.doi.org/10.1038/s41380-018-0258-3DOI Listing

Publication Analysis

Top Keywords

alzheimer's disease
8
clinical phenotype
8
mapttyrobp mice
8
mice despite
8
learning behavior
8
integrative approach
4
approach sporadic
4
sporadic alzheimer's
4
disease deficiency
4
deficiency tyrobp
4

Similar Publications

Background: Research has shown that engaging in a range of healthy lifestyles or behavioral factors can help reduce the risk of developing dementia. Improved knowledge of modifiable risk factors for dementia may help engage people to reduce their risk, with beneficial impacts on individual and public health. Moreover, many guidelines emphasize the importance of providing education and web-based resources for dementia prevention.

View Article and Find Full Text PDF

With the increasing number of patients with Alzheimer's Disease (AD), the demand for early diagnosis and intervention is becoming increasingly urgent. The traditional detection methods for Alzheimer's disease mainly rely on clinical symptoms, biomarkers, and imaging examinations. However, these methods have limitations in the early detection of Alzheimer's disease, such as strong subjectivity in diagnostic criteria, high detection costs, and high misdiagnosis rates.

View Article and Find Full Text PDF

Influence of lung function on macro- and micro-structural brain changes in mid- and late-life.

Int J Surg

January 2025

Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Introduction: Lung function has been associated with cognitive decline and dementia, but the extent to which lung function impacts brain structural changes remains unclear. We aimed to investigate the association of lung function with structural macro- and micro-brain changes across mid- and late-life.

Methods: The study included a total of 37 164 neurologic disorder-free participants aged 40-70 years from the UK Biobank, who underwent brain MRI scans 9 years after baseline.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive decline. Despite extensive research, therapeutic options remain limited. Varenicline, an αβ nicotinic acetylcholine receptor agonist, shows promise in enhancing cognitive function.

View Article and Find Full Text PDF

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented.

View Article and Find Full Text PDF

Want 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!