Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer ’s disease

AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disease in which the formation of extracellular aggregates of amyloid beta (Aβ) peptide, fibrillary tangles of intraneuronal tau and microglial activation are major pathological hallmarks. One of the key molecules involved in microglial activatio n is galectin-3 (gal3), and we demonstrate here for the first time a key role of gal3 in AD pathology. Gal3 was highly upregulated in the brains of AD patients and 5xFAD (familial Alzheimer’s disease) mice and found specifically expressed in microglia associated with Aβ plaques. Single-nucleotide polymorphisms in theLGALS3 gene, which encodes gal3, were associated with an increased risk of AD. Gal3 deletion in 5xFAD mice attenuated microglia-associated immune responses, particularly those associated with TLR and TREM2/DAP12 signaling. In vitro data revealed that gal3 was required to fully activate microglia in response to fibrillar A β. Gal3 deletion decreased the Aβ burden in 5xFAD mice and improved cognitive behavior. Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in WT mice was sufficient to induce the formation of long-lasting (2 months) insoluble Aβ aggregates, which were absent when gal3 was lacking. High-resolution microscopy (stochastic optical reconstruction microscopy) demonstrated close colocalization of gal3 and TREM2 in microglial processes, and a direct interaction was sh...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Source: Neuropsychiatric Disease and Treatment - Category: Psychiatry Tags: Neuropsychiatric Disease and Treatment Source Type: research
A proof-of-concept study shows regular aerobic exercise may prevent or slow cognitive decline in older adults at risk for Alzheimer's.
Source: CNN.com - Health - Category: Consumer Health News Source Type: news
Grants for research on the outcomes of care for persons with Alzheimer's disease and related dementia by identifying home- and community-based services used, as well as barriers to accessing care and unmet needs. Explaining geographic disparities, such as urban versus rural, in access to and quality of care is a suggested research topic. Geographic coverage: Nationwide -- National Institute on Aging, National Institutes of Health, U.S. Department of Health and Human Services
Source: Funding opportunities via the Rural Health Information Hub - Category: American Health Source Type: funding
This study brings us one step closer toward teasing out the effects in people with biomarker defined Alzheimer’s.” While the study results must be replicated in much larger studies, Zhang suggested that anyone concerned about cognitive decline or Alzheimer’s consider adding exercise to their daily lives. While it’s best to start exercising early in life, he said, “it is not too late to receive the benefits of exercise even late in life when there are already amyloid clumps in the brain.” The-CNN-Wire &© 2019 Cable News Network, Inc., a Time Warner Company. All rights reserved.
Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Health News Syndicated CBSN Boston Alzheimer's Disease CNN Source Type: news
Authors: Randolph C Abstract Correctly diagnosing early symptomatic Alzheimer disease in the context of multinational clinical trials poses a significant challenge. Subjective complaints of memory are fairly ubiquitous in an older population, and establishing the presence of definitive cognitive decline from clinical assessments is difficult. Most such trials have adopted the use of standardized episodic memory measures as an inclusion criterion, typically setting the cutoff at one standard deviation below age normal means. This is useful in terms of establishing the presence of an objective impairment of memory, t...
Source: The American Journal of Geriatric Psychiatry - Category: Psychiatry Tags: Am J Geriatr Psychiatry Source Type: research
Chalcones are compounds with wide interesting biological activities including Alzheimer ’ s disease. A comparative study was performed between the chalcones (E)-1-(2-aminophenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one and 1-(6-amino-1,3-benzodioxol-5-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one regarding the influence of benzodioxol group on their molecular conformations. The first chalcone was neutralized with dilute hydrochloric acid, while solid of the second was filtered and recrystallized from ethanol, both on centrosymmetric space group P21/c. Their molecular packing were evaluated by Hirshfeld surfaces, an...
Source: Journal of the Brazilian Chemical Society - Category: Chemistry Source Type: research
Coming out next month is yet another book on how to avoid living with late-stage dementia. The title says it all: "O, Let Me Not Get Alzheimer's, Sweet Heaven!" This demand motivates much of my research on VSED. Hardly a day goes by without some newspaper story, personal memoir or medical report referring to Alzheimer’s Disease, arousing personal fears or memories of relatives and friends whose lives have been changed permanently by this condition. Grim as it is to suffer the ravages of this disease, many people are as concerned about the last few years and months of life as an Alzheimer’s patient as ...
Source: blog.bioethics.net - Category: Medical Ethics Authors: Tags: Health Care syndicated Source Type: blogs
Alzheimer’s disease (AD) is the most common type of dementia worldwide. The deposition of amyloid β (Aβ) is one of the most important pathological changes in AD. Autophagy, which mediates degradation of toxic proteins and maintains normal neuronal function, is dysfunctional in AD; dysfunctional autophagy is believed to be a critical pathological feature of AD. Here, we evaluated the in vitro and in vivo effects of a traditional Chinese medicinal formula called Yizhiqingxin formula (YQF) on autophagy. We determined that treatment with a high dose of YQF improved spatial memory and decreased the hippocampal A...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
We describe how careful data unification, time-alignment, and imputation techniques can handle missing data rates inherent in real-world settings and ultimately show utility of these disparate data in differentiating symptomatics from healthy controls based on features computed purely from device data. The Study in Context: The FDA creates new Digital Health unit to reimagine regulatory paths in the age of scalable, AI-enhanced innovation Five reasons the future of brain enhancement is digital, pervasive and (hopefully) bright Mindstrong Health identifies digital biomarkers of cognitive function using smartphone data Neu...
Source: SharpBrains - Category: Neuroscience Authors: Tags: Cognitive Neuroscience Health & Wellness Technology Alzheimers-disease Apple behavioral cognitive decline dementia Eli Lilly Evidation healthcare HIPAA mental-decline mild-cognitive-impairment physiological Source Type: blogs
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