scholarly journals Neurogranin and Neuronal Pentraxin Receptor as Synaptic Dysfunction Biomarkers in Alzheimer’s Disease

2021 ◽  
Vol 10 (19) ◽  
pp. 4575
Author(s):  
Maciej Dulewicz ◽  
Agnieszka Kulczyńska-Przybik ◽  
Agnieszka Słowik ◽  
Renata Borawska ◽  
Barbara Mroczko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Synaptic Proteins ◽  
Synaptic Dysfunction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Synaptic Loss ◽  
Neuronal Pentraxin ◽  
The Relationship ◽  
Xmap Technology

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the early stage of the disease. To our best knowledge, this is the first study that analyzes the CSF concentrations of two synaptic proteins together, such as neurogranin (Ng) and neuronal pentraxins receptor (NPTXR) in relation to neurochemical dementia biomarkers in Alzheimer’s disease. Methods: Ng, NPTXR and classical AD biomarkers concentrations were measured in the CSF of patients with AD and non-demented controls (CTRL) using an enzyme-linked immunosorbent assay (ELISA) and Luminex xMAP technology. Results: The CSF level of Ng was significantly higher, whereas the NPTXR was significantly lower in the AD patients than in cognitively healthy controls. As a first, we calculated the NPTXR/Ng ratio as an indicator of synaptic disturbance. The patients with AD presented a significantly decreased NPTXR/Ng ratio. The correlation was observed between both proteins in the AD and the whole study group. Furthermore, the relationship between the Ng level and pTau181 was found in the AD group of patients. Conclusions: The Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD.

scholarly journals Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3261
Author(s):  
Xiao Liu ◽  
Qian Zhou ◽  
Jia-He Zhang ◽  
Xiaoying Wang ◽  
Xiumei Gao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Disease Model ◽  
Amyloid Β ◽  
Brain Lesions ◽  
Synaptic Dysfunction ◽  
Synaptic Loss ◽  
And Function ◽  
The Brain

Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.

Molecular Insight into the Crosstalk of UPS Components and Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1193-1201
Author(s):  
Abdullah Al Mamun ◽  
Md. Mosiqur Rahman ◽  
Sonia Zaman ◽  
Mst Shirajum Munira ◽  
Md. Sahab Uddin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Early Stage ◽  
Therapeutic Interventions ◽  
Cellular Proteins ◽  
Synaptic Dysfunction ◽  
Main Components ◽  
The Relationship ◽  
Insight Into

: The ubiquitin (Ub)-proteasome system (UPS) targets various cellular proteins for degradation. It has been found that defects in the UPS play a crucial role in the pathogenesis of Alzheimer's disease (AD), as the existence of Ub immunoreactivity in AD-linked neuronal inclusions, including neurofibrillary tangles, is observed in all types of AD cases. Current investigations have shown that components of the UPS can be connected with the early stage of AD, which is characterized by synaptic dysfunction, and to the late phases of the disease, marked by neurodegeneration. Although the significance of UPS in the pathogenesis of AD has been emphasized, targeted treatment at the main components of these pathways has a great perspective in advancing new therapeutic interventions for AD. In this review, we emphasize the relationship between UPS and AD pathology. We also represent the recent therapeutic advancements targeting UPS components in AD.

scholarly journals Antioxidant Therapies for Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Ye Feng ◽  
Xiaochuan Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Senile Plaques ◽  
Toxic Substances ◽  
Synaptic Loss ◽  
Recent Developments ◽  
Multiple Cell ◽  
Future Potential ◽  
And Behavior

Alzheimer’s disease (AD) is the most common neurodegenerative disease featuring progressive impairments in memory, cognition, and behavior and ultimately leads to death. The histopathological changes of Alzheimer’s disease include neuronal and synaptic loss, formation of extracellular senile plaques and intracellular neurofibrillary tangles in brain. Multiple lines of evidence indicate that oxidative stress not only strongly participates in an early stage of Alzheimer’s disease prior to cytopathology, but plays an important role in inducing and activating multiple cell signaling pathways that contribute to the lesion formations of toxic substances and then promotes the development of Alzheimer’s disease. Many years of studies show that antioxidant therapies have enjoyed general success in preclinical studies. Therefore, this paper mainly focuses on the recent developments of common used antioxidant therapies for Alzheimer’s disease and thus provides indications for future potential antioxidant therapeutic strategies of neurodegenerative diseases.

Differential loss of synaptic proteins in Alzheimer's disease: Implications for synaptic dysfunction

2005 ◽  
Vol 7 (2) ◽  
pp. 103-117 ◽  
Author(s):  
P. Hemachandra Reddy ◽  
Geethalakshmi Mani ◽  
Byung S. Park ◽  
Joline Jacques ◽  
Geoffrey Murdoch ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Proteins ◽  
Synaptic Dysfunction

scholarly journals Sulfhydration of AKT triggers Tau-phosphorylation by activating glycogen synthase kinase 3β in Alzheimer’s disease

2020 ◽  
Vol 117 (8) ◽  
pp. 4418-4427
Author(s):  
Tanusree Sen ◽  
Pampa Saha ◽  
Tong Jiang ◽  
Nilkantha Sen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Early Stage ◽  
Underlying Mechanism ◽  
Glycogen Synthase Kinase ◽  
Synaptic Dysfunction ◽  
Glycogen Synthase Kinase 3Β ◽  
Phosphorylated Akt ◽  
Postmortem Brains

In Alzheimer’s disease (AD), human Tau is phosphorylated at S199 (hTau-S199-P) by the protein kinase glycogen synthase kinase 3β (GSK3β). HTau-S199-P mislocalizes to dendritic spines, which induces synaptic dysfunction at the early stage of AD. The AKT kinase, once phosphorylated, inhibits GSK3β by phosphorylating it at S9. In AD patients, the abundance of phosphorylated AKT with active GSK3β implies that phosphorylated AKT was unable to inactivate GSK3β. However, the underlying mechanism of the inability of phosphorylated AKT to phosphorylate GSK3β remains unknown. Here, we show that total AKT and phosphorylated AKT was sulfhydrated at C77 due to the induction of intracellular hydrogen sulfide (H2S). The increase in intracellular H2S levels resulted from the induction of the proinflammatory cytokine, IL-1β, which is a pathological hallmark of AD. Sulfhydrated AKT does not interact with GSK3β, and therefore does not phosphorylate GSK3β. Thus, active GSK3β phosphorylates Tau aberrantly. In a transgenic knockin mouse (AKT-KI+/+) that lacked sulfhydrated AKT, the interaction between AKT or phospho-AKT with GSK3β was restored, and GSK3β became phosphorylated. In AKT-KI+/+ mice, expressing the pathogenic human Tau mutant (hTau-P301L), the hTau S199 phosphorylation was ameliorated as GSK3β phosphorylation was regained. This event leads to a decrease in dendritic spine loss by reducing dendritic localization of hTau-S199-P, which improves cognitive dysfunctions. Sulfhydration of AKT was detected in the postmortem brains from AD patients; thus, it represents a posttranslational modification of AKT, which primarily contributes to synaptic dysfunction in AD.

Role of Thiamine in Alzheimer's Disease

2011 ◽  
Vol 26 (8) ◽  
pp. 588-598 ◽  
Author(s):  
Khanh vinh quốc Lu’o’ng ◽  
Lan Thi Hoàng Nguyễn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Pyruvate Dehydrogenase Complex ◽  
Peripheral Tissues ◽  
Elderly Individuals ◽  
Promoter Gene ◽  
Progressive Neurodegeneration ◽  
The Relationship

Alzheimer’s disease (AD) is the most common form of dementia in elderly individuals and is associated with progressive neurodegeneration of the human neocortex. Thiamine levels and the activity of thiamine-dependent enzymes are reduced in the brains and peripheral tissues of patients with AD. Genetic studies have provided the opportunity to determine what proteins link thiamine to AD pathology (ie, transketolase, apolipoprotein E, α-1-antitrypsin, pyruvate dehydrogenase complex, p53, glycogen synthetase kinase-3β, c-Fos gene, the Sp1 promoter gene, and the poly(ADP-ribosyl) polymerase-1 gene). We reviewed the association between histopathogenesis and neurotransmitters to understand the relationship between thiamine and AD pathology. Oral thiamine trials have been shown to improve the cognitive function of patients with AD; however, absorption of thiamine is poor in elderly individuals. In the early stage of thiamine-deficient encephalopathy (Wernicke’s encephalopathy), however, parental thiamine has been used successfully. Therefore, further studies are needed to determine the benefits of using parental thiamine as a treatment for AD.

scholarly journals Lifelong Bilingualism Functions as an Alternative Intervention for Cognitive Reserve Against Alzheimer's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Haiqing Liu ◽  
Longhuo Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Cognitive Reserve ◽  
Early Stage ◽  
Brain Network ◽  
Pharmacological Intervention ◽  
Alternative Intervention ◽  
Confounding Variables ◽  
The Relationship

Bilingualism has been reported to significantly delay the onset of dementia and plays an important role in the management of Alzheimer's disease (AD), a condition inducing impairment in the brain network and cognitive decline. Cognitive reserve is associated with the adaptive maintenance of neural functions by protecting against neuropathology. Bilingualism acts as a beneficial environmental factor contributing to cognitive reserve, although some potential confounding variables still need further elucidation. In this article, the relationship between bilingualism and cognitive reserve is discussed, interpreting the advantage of bilingualism in protecting against cognitive decline. In addition, the possible brain and biochemical mechanisms, supporting the advantageous effects of bilingualism in delaying the onset of dementia, involved in bilingualism are reviewed. Effectively, bilingualism can be considered as a pharmacological intervention with no side effects. However, the investigation of the pharmacological parameters of bilingualism is still at an early stage.

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