The role of the phosphoinositide signalling system in the pathogenesis of sporadic Alzheimer's disease: a hypothesis

1997 ◽  
Vol 25 (3) ◽  
pp. 373-380 ◽  
Author(s):  
Christopher J Fowler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sporadic Alzheimer’S Disease ◽  
Signalling System

The Role of Microglia in Sporadic Alzheimer’s Disease

2021 ◽  
Vol 79 (3) ◽  
pp. 961-968
Author(s):  
Wolfgang J. Streit ◽  
Habibeh Khoshbouei ◽  
Ingo Bechmann
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Genetic Mutations ◽  
Sporadic Alzheimer’S Disease ◽  
Immune Effector ◽  
Effector Cells ◽  
Immune Effector Cells ◽  
Amyloid Cascade

Microglia constitute the brain’s immune system and their involvement in Alzheimer’s disease has been discussed. Commonly, and in line with the amyloid/neuroinflammation cascade hypothesis, microglia have been portrayed as potentially dangerous immune effector cells thought to be overactivated by amyloid and producing neurotoxic inflammatory mediators that lead to neurofibrillary degeneration. We disagree with this theory and offer as an alternative the microglial dysfunction theory stating that microglia become impaired in their normally neuroprotective roles because of aging, i.e., they become senescent and aging neurons degenerate because they lack the needed microglial support for their survival. Thus, while the amyloid cascade theory relies primarily on genetic data, the dysfunction theory incorporates aging as a critical etiological factor. Aging is the greatest risk factor for the sporadic (late-onset) and most common form of Alzheimer’s disease, where fully penetrant genetic mutations are absent. In this review, we lay out and discuss the human evidence that supports senescent microglial dysfunction and conflicts with the amyloid/neuroinflammation idea.

scholarly journals P1-345: Role of Vitamin D Signaling in Sporadic Alzheimer’s Disease: A Clinico-Experimental Study

2016 ◽  
Vol 12 ◽  
pp. P561-P562
Author(s):  
Anindita Banerjee ◽  
Vineet Kumar Khemka ◽  
Debashree Roy ◽  
Aparajita Dhar ◽  
Tapan Kumar Sinha Roy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Experimental Study ◽  
Vitamin D ◽  
Sporadic Alzheimer’S Disease ◽  
Vitamin D Signaling

The modulatory role of phloretin in Aβ25–35 induced sporadic Alzheimer’s disease in rat model

2018 ◽  
Vol 392 (3) ◽  
pp. 327-339 ◽  
Author(s):  
Priya J. Ghumatkar ◽  
Sachin P. Patil ◽  
Vaibhavi Peshattiwar ◽  
Tushara Vijaykumar ◽  
Vikas Dighe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Sporadic Alzheimer’S Disease

P1-046: ROLE OF PLD3 RARE VARIANTS IN EUROPEAN SPORADIC ALZHEIMER'S DISEASE PATIENTS

2014 ◽  
Vol 10 ◽  
pp. P319-P320
Author(s):  
Alfredo Ramirez ◽  
Stefanie Heilmann ◽  
Dmitriy Drichel ◽  
Isabel Hernandez ◽  
Alberto Lleó ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rare Variants ◽  
Sporadic Alzheimer’S Disease

scholarly journals The Role of BMI1 in Late-Onset Sporadic Alzheimer’s Disease

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 825
Author(s):  
Ryan Hogan ◽  
Anthony Flamier ◽  
Eleonora Nardini ◽  
Gilbert Bernier
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Single Gene ◽  
Short Review ◽  
Sporadic Alzheimer’S Disease ◽  
Mendelian Genetics ◽  
Bmi1 Expression

Late-onset sporadic Alzheimer’s disease (LOAD) seems to contain a “hidden” component that cannot be explained by classical Mendelian genetics, with advanced aging being the strongest risk factor. More surprisingly, whole genome sequencing analyses of early-onset sporadic Alzheimer’s disease cohorts also revealed that most patients do not present classical disease-associated variants or mutations. In this short review, we propose that BMI1 is possibly epigenetically silenced in LOAD. Reduced BMI1 expression is unique to LOAD compared to familial early-onset AD (EOAD) and other related neurodegenerative disorders; moreover, reduced expression of this single gene is sufficient to reproduce most LOAD pathologies in cellular and animal models. We also show the apparent amyloid and Tau-independent nature of this epigenetic alteration of BMI1 expression. Lastly, examples of the mechanisms underlying epigenetic dysregulation of other LOAD-related genes are also illustrated.

Liver-Brain Axis in Sporadic Alzheimer’s Disease: Role of Ten Signature Genes in a Mouse model

2020 ◽  
Vol 19 ◽  
Author(s):  
Ruchi Jakhmola-Mani ◽  
Anam Islam ◽  
Deepshikha Pande Katare
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cholesterol Biosynthesis ◽  
Brain Diseases ◽  
Entire Body ◽  
Junk Food ◽  
Acid Modification ◽  
Sporadic Alzheimer’S Disease ◽  
Nutritional Effect

Aim:: Poor nutritional effect of junk food induces injurious adversities to the liver and brain but still most of the developing nations survives on these diets to compensate for fast-paced lifestyle. Aim of the study is to infer the proteinconnections behind liver-brain axis and identify the role of these proteins in causing neurodegenerative disorders. Background: : Chronic consumption of fructose and fat rich food works as a toxin in body and have the ability to cause negative metabolic shift. Recently a study was published in Annals of Internal Medicine (2019) citing the loss of vision and hearing in a 14-year-old boy whose diet was strictly restricted to fries and junk-food for almost a decade. This puts the entire body on insulin resistance and related co-morbidities and causes simultaneous damaging effects in liver as well brain. This work provides insights into liver-brain axis and explains how liver is involved in brain related disorders. Objective: : In this study transcriptomic data relating to chronic eating of junk-food was analyzed and simultaneous damage that happens in liver and brain was assessed at molecular level. Method:: Transcriptomic study was taken from GEO database and analysed to find out the genes dysregulated in both liver and brain during this metabolic stress. Cytoscapev3.7 was used to decipher the signalling between liver and brain. This connection between both was called as Liver-Brain axis. Results : The results obtained from our study indicates the role of TUBB5-HYOU1-SDF2L1-DECR1-CDH1-EGFR-SKP2- SOD1-IRAK1-FOXO1 gene signature towards the decline of concurrent liver and brain health. Dysregulated levels of these genes are linked to molecular processes like cellular senescence, hypoxia, glutathione synthesis, amino acid modification, increased nitrogen content, synthesis of BCAAs, cholesterol biosynthesis, steroid hormone signalling and VEGF pathway. Conclusion: We strongly advocate that prolonged consumption of junk food is a major culprit in brain related disorders like Alzheimer’s disease and propose that receptors for brain diseases lie outside the brain and aiming them for drug discovery and design may be beneficial in future clinical studies. This study also discusses the connection between NAFLD (nonalcoholic fatty liver disease) and sAD (sporadic Alzheimer’s disease) owing to liver-brain axis.

scholarly journals DIVERGENT EFFECT OF CENTRAL INCRETIN RECEPTORS INHIBITION IN A RAT MODEL OF SPORADIC ALZHEIMER'S DISEASE

2021 ◽  
Author(s):  
Jelena Osmanovic Barilar ◽  
Ana Knezovic ◽  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Melita Salkovic-Petrisic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Cell Metabolism ◽  
Hormone Secretion ◽  
Gastric Inhibitory Polypeptide ◽  
Brain Cell ◽  
Sporadic Alzheimer’S Disease ◽  
The Brain

The incretin system is an emerging new field that might provide valuable contributions to the research of both pathophysiology and therapeutic strategies in the treatment of diabetes, obesity, and neurodegenerative disorders. This study aimed to explore the role of central glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) on cell metabolism and energy in the brain as well as on the levels of these incretins, insulin and glucose, by inhibiting the central incretins' receptors following intracerebroventricular administration of the respective antagonists in healthy rats and a streptozotocin-induced rat model of sporadic Alzheimer's disease (sAD). Chemical ablation of the central GIP receptor (GIPR) or GLP-1 receptor (GLP-1R) in healthy and diseased animals indicated a region-dependent role of incretins in the brain cell energy and metabolism and central incretin-dependent modulation of peripheral hormone secretion, markedly after GIPR inhibition, as well as a dysregulation of the GLP-1 system in experimental sAD.

The Association between TNF-alpha, IL-1 alpha and IL-10 with Alzheimer's Disease

2020 ◽  
Vol 17 ◽  
Author(s):  
Marija Culjak ◽  
Matea Nikolac Perkovic ◽  
Suzana Uzun ◽  
Dubravka Svob Strac ◽  
Gordana Nedic Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Tnf Alpha ◽  
Similar Distribution ◽  
Serum Concentrations ◽  
Sporadic Alzheimer’S Disease ◽  
Neuroinflammatory Response ◽  
Tnf Α

Background: Sporadic Alzheimer’s Disease (AD) is assumed to be associated with different biological/genetic vulnerability, as well as with neuroinflammation, mediated by cytokines. The present study evaluated the role of cytokines in AD. Objective: Aim was to determine the possible association of TNF-α (rs1800629), IL1-α (rs1800587) and IL-10 (rs1800896) polymorphisms with AD, and to assess serum TNF-α, IL-1α and IL-10 concentrations in patients with AD and in subjects with mild cognitive impairment (MCI). Method: The study included 645 Caucasian participants: 395 subjects with AD and 250 subjects with MCI. Genotyping was performed using real time PCR in all 645 subjects, while serum concentrations of TNF-α, IL-1α and IL-10 and were determined using ELISA in 174 subjects. Results: The frequency of the TNF-ɑ rs1800629, IL1-ɑ rs1800587 or IL-10 rs1800896 genotypes did not differ significantly between patients with AD and MCI. Serum concentration of IL-1α and IL-10 were significantly decreased, while the concentration of TNF-α was significantly higher in patients with AD than in MCI subjects. TNF-α, IL1-α or IL-10 concentrations were similar in subjects with AD or MCI subdivided into carriers of the corresponding TNF-ɑ rs1800629, IL1-ɑ rs1800587 or IL-10 rs1800896 genotypes. Conclusions: Similar distribution of the IL1-ɑ rs1800587, TNF-ɑ rs1800629 or IL-10 rs1800896 genotypes in subjects with AD and MCI failed to confirm that these specific risk genotypes are associated with vulnerability to develop AD. Alteration in IL-1α, IL-10 and TNF-α concentrations in patients with AD partially confirmed the association with neuroinflammatory response in AD.

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