scholarly journals Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention

2021 ◽  
Vol 15 ◽  
Author(s):  
Guimei Zhang ◽  
Zicheng Wang ◽  
Huiling Hu ◽  
Meng Zhao ◽  
Li Sun
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Interventions ◽  
Tau Pathology ◽  
Age Related ◽  
Amyloid Accumulation ◽  
Pathophysiological Role ◽  
Inflammatory Drugs ◽  
Β Amyloid

Alzheimer’s disease (AD) is one of the most common types of age-related dementia worldwide. In addition to extracellular amyloid plaques and intracellular neurofibrillary tangles, dysregulated microglia also play deleterious roles in the AD pathogenesis. Numerous studies have demonstrated that unbridled microglial activity induces a chronic neuroinflammatory environment, promotes β-amyloid accumulation and tau pathology, and impairs microglia-associated mitophagy. Thus, targeting microglia may pave the way for new therapeutic interventions. This review provides a thorough overview of the pathophysiological role of the microglia in AD and illustrates the potential avenues for microglia-targeted therapies, including microglial modification, immunoreceptors, and anti-inflammatory drugs.

Role of TREM2 in Alzheimer's Disease and its Consequences on β- Amyloid, Tau and Neurofibrillary Tangles

2020 ◽  
Vol 16 (13) ◽  
pp. 1216-1229 ◽  
Author(s):  
Anurag K. Singh ◽  
Gaurav Mishra ◽  
Anand Maurya ◽  
Rajendra Awasthi ◽  
Komal Kumari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Tau Pathology ◽  
Functional Roles ◽  
Age Related ◽  
Β Amyloid ◽  
The Impact ◽  
Neuronal Stress

: Alzheimer's Disease (AD) is age-related neurodegenerative disorder recognized by a steadily gradual cognitive decline that has devastating personal and socioeconomic implications. Recently, some genetic factors for AD have been identified which attracted wide attention of researchers in different areas of AD biology and possible new therapeutic targets. Alternative forms of triggering receptor expressed on myeloid cells 2 (TREM2) genes are examples of such risk factors, which contribute higher risk for developing AD. Comprehending TREM2 function pledge to provide salient insight into how neuroinflammation contributes to AD pathology. The dearth of microglial TREM2 shepherd to augmented tau pathology is couple with frequent enhancement of activated neuronal stress kinases. The involvement of TREM2 in the regulation of tau-associated innate immune response of the CNS has clearly demonstrated through these findings. However, whether decrease level of TREM2 assists pathology of tau through changed clearance and pathological escalation of tau or through direct contact between microglia and neuron and any alternative possible mechanisms need to examine. This review briefly summarizes distinct functional roles of TREM2 in AD pathology and highlights the TREM2 gene regulation. We have also addressed the impact of TREM2 on β-amyloid plaques and tau pathology in Alzheimer’s disease.

scholarly journals THE ROLE OF METABOLIC SYNDROME IN THE ALZHEIMER’S DISEASE

2021 ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome ◽  
Therapeutic Interventions ◽  
The Metabolic Syndrome ◽  
Age Related ◽  
Therapeutic Measures ◽  
Β Amyloid

INTRODUCTION Alzheimer’s disease (AD) is characterized by progressive cognitive loss coupled with age-related functional impairment. Its two major brands are β-amyloid plaques and neurofibrillary tangles. There is strong evidence for a relationship between Metabolic Syndrome (MS) and AD. Both pathologies are quite prevalent and dependent on aging. OBJECTIVE The present study seeks to understand the role of the metabolic syndrome in the pathophysiology of Alzheimer’s disease and to describe preventive and therapeutic interventions. METHODOLOGY The review was made based on the search for scientific articles in the electronic databases PUBMED and Web of Science, using the descriptors “Alzheimer’s Disease”, “Metabolic Syndrome” DISCUSSION MS is a metabolic breakdown with the potential to damage insulin signaling in the brain, causing insulin resistance, inhibiting β-amyloid clearance and its accumulation, which generates neuroinflammation. In addition, it induces a prothrombotic state with ischemic effects, resulting in oxidative stress and neuroinflammation and progressive local brain atrophies. The components of the metabolic syndrome are related to AD, exacerbating neuroinflammation and insulin resistance. Preventive and therapeutic measures aiming at the MS are promising. CONCLUSION From the analyzes developed in this study, different relationships between the components of MS and AD are perceived, the first being possible causes and / or effects of the second. Since insulin resistance plays a major role in the initiation and perpetuation of cognitive impairment in AD. Furthermore, the components of MS associated with AD, when treated with preventive and therapeutic measures, break this association by promoting rebalancing of the metabolism.

scholarly journals Alzheimer’s disease and the genetics of neuroprotection

2020 ◽  
Author(s):  
Tyler Johnson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Underlying Mechanism ◽  
Therapeutic Interventions ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Pathogenic Variants ◽  
Age Related ◽  
Β Amyloid ◽  
Reduced Risk

As the world’s leading form of age-related dementia, Alzheimer’s disease (AD) is a devastating neurological disorder associated with severe emotional and economic burdens. Despite years of research, the underlying mechanism behind this disease remains unclear. The current prevailing theory relies on the deposition of toxic amyloid beta (Aβ), which promotes the formation of phosphorylated tau tangles, and together these damaging changes drive the loss of neurons. Much of AD development can be attributed to genetic influences, including pathogenic variants of β-amyloid precursor protein, presenilins 1 and 2, and the presence of apolipoprotein 4. However, there are other subtle, yet significant variations within our genome that contribute to protecting us against AD. Variants of the phospholipase Cγ2 and toll-like receptor 4 genes have been associated with reduced risk of developing AD, as well as increased longevity of patients. These neuroprotective variants can guide the development of future therapeutic interventions for AD, as current strategies have proven lackluster.

Alzheimer’s disease pathogenesis is dependent on neuronal receptor PTPσ

2016 ◽  
Author(s):  
Yuanzheng Gu ◽  
Yaoling Shu ◽  
Angela W. Corona ◽  
Kui Xu ◽  
Allen F. Yi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Behavioral Deficits ◽  
Amyloid Accumulation ◽  
Β Amyloid ◽  
Neuronal Receptor ◽  
Tau Aggregation

β-amyloid accumulation and Tau aggregation are hallmarks of Alzheimer’s disease, yet their underlying molecular mechanisms remain obscure, hindering therapeutic advances. Here we report that neuronal receptor PTPσ mediates both β-amyloid and Tau pathogenesis in two mouse models. In the brain, PTPσ binds to β-amyloid precursor protein (APP). Depletion of PTPσ reduces the affinity between APP and β-secretase, diminishing APP proteolytic products by β- and γ-cleavage without affecting other major substrates of the secretases, suggesting a specificity of β-amyloidogenic regulation. In human APP transgenic mice during aging, the progression of β-amyloidosis, Tau aggregation, neuroinflammation, synaptic loss, as well as behavioral deficits, all show unambiguous dependency on the expression of PTPσ. Additionally, the aggregates of endogenous Tau are found in a distribution pattern similar to that of early stage neurofibrillary tangles in Alzheimer brains. Together, these findings unveil a gatekeeping role of PTPσ upstream of the degenerative pathogenesis, indicating a potential for this neuronal receptor as a drug target for Alzheimer’s disease.

scholarly journals Non-Steroidal Anti-Inflammatory Drugs in Alzheimer's Disease and Parkinson's Disease: Reconsidering the Role of Neuroinflammation

2010 ◽  
Vol 3 (6) ◽  
pp. 1812-1841 ◽  
Author(s):  
Amy H. Moore ◽  
Matthew J. Bigbee ◽  
Grace E. Boynton ◽  
Colin M. Wakeham ◽  
Hilary M. Rosenheim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals Inverse Correlation Between Alzheimer’s Disease and Cancer: Short Overview

2021 ◽  
Author(s):  
Agnieszka Zabłocka ◽  
Wioletta Kazana ◽  
Marta Sochocka ◽  
Bartłomiej Stańczykiewicz ◽  
Maria Janusz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Kinase Inhibitor ◽  
Fungal Infections ◽  
Neurological Diseases ◽  
Inverse Correlation ◽  
Biological Mechanisms ◽  
Age Related ◽  
Common Risk Factors

AbstractThe negative association between Alzheimer’s disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much attention is also paid to the potential impact of chronic viral, bacterial, and fungal infections that are responsible for the inflammatory pathway in AD and also play a key role to cancer development. New data about common mechanisms in etiopathology of cancer and neurological diseases suggests new therapeutic strategies. Among them, the use of nilotinib, tyrosine kinase inhibitor, protein kinase C, and bexarotene is the most promising.

scholarly journals Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

2021 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Randall Bateman ◽  
Ruben Smith ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Β Amyloid ◽  
Tau Pet ◽  
Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

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