Amyloid-β and Phosphorylated Tau are the Key Biomarkers and Predictors of Alzheimer’s Disease

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Alzheimer's disease (AD) is a age-related neurodegenerative and major public health concern both in Texas, US Worldwide. This mainly characterized by amyloid-beta (Aβ) phosphorylated Tau (p-Tau) accumulation the brains of patients with AD increasing evidence suggests that these are key biomarkers AD. Both Aβ p-tau can be detected through various imaging techniques (such as positron emission tomography, PET) cerebrospinal fluid (CSF) analysis. The presence individuals, who asymptomatic or have mild cognitive impairment indicate an increased risk developing future. Furthermore, combination often used for more accurate diagnosis prediction progression. Along being disease, it associated other chronic conditions such cardiovascular obesity, depression, diabetes because studies shown comorbid make people vulnerable to In first part this review, we discuss biofluid-based Aβ, p-Tau & plasma could alternative sensitive technique diagnose second part, underlying molecular mechanisms linked how they affect clinical care.

Language: Английский

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Alzheimer’s disease and clinical trials

Journal of Basic and Clinical Physiology and Pharmacology, Journal Year: 2024, Volume and Issue: 35(1-2), P. 31 - 44

Published: Jan. 1, 2024

Abstract Alzheimer’s disease (AD) is spreading its root disproportionately among the worldwide population. Many genes have been identified as hallmarks of AD. Based upon knowledge, many clinical trials designed and conducted. Attempts made to alleviate pathology associated with AD by targeting molecular products these genes. Irrespective understanding on genetic component AD, failed imposed greater challenges path drug discovery. Therefore, this review aims identify research articles pinpoint limitations candidates (thiethylperazine, CT1812, crenezumab, CNP520, lecanemab), which are under or withdrawn from trials. Thorough analysis cross-talk pathways led identification confounding factors, could interfere success such thiethylperazine, CNP520. Though were enrolled in trials, yet literature shows limitations. These raise questions rationale behind enrollments A meticulous prior assessment outcome studies may stop risky at their inceptions. This save time, money, resources.

Language: Английский

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Inducing Agents for Alzheimer’s Disease in Animal Models

Journal of Exploratory Research in Pharmacology, Journal Year: 2024, Volume and Issue: 000(000), P. 000 - 000

Published: July 16, 2024

The most prevalent form of dementia, Alzheimer's disease (AD), is a neurological disorder that causes gradual memory loss. AD characterized by amyloid-beta plaques, neurofibrillary tangles, and neuron While preclinical clinical trials are underway to reduce the generation overall brain load, current treatment focuses on alleviating symptoms. Animal studies essential for advancing our understanding AD, identifying potential drug targets, testing experimental therapies. An ideal animal model not only exhibits same symptoms pathological changes as human but also follows sequence events. This review highlights various inducing agents used in animals, such streptozotocin, aluminium chloride, trimethyltin, lipopolysaccharide, scopolamine, others, along with their underlying mechanisms. outcomes some develop discussed briefly. Among chemically induced models, streptozotocin frequently used, while d-galactose, aluminium-induced models being because they non-invasive, reproducible, compatible. However, none chemical/drug-induced fully capture scope pathology cognitive impairment. Overall, further research necessary establish stability terms consistency reproducibility.

Language: Английский

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Proteomics of the astrocyte secretome reveals changes in their response to soluble oligomeric Aβ

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 166(2), P. 346 - 366

Published: June 11, 2023

Abstract Astrocytes associate with amyloid plaques in Alzheimer's disease (AD). react to changes the brain environment, including increasing concentrations of amyloid‐β (Aβ). However, precise response astrocytes soluble small Aβ oligomers at similar those present human has not been addressed. In this study, we exposed media from neurons that express precursor protein ( APP) transgene double Swedish mutation (APPSwe), and which contains APP‐derived fragments, oligomers. We then used proteomics investigate astrocyte secretome. Our data show dysregulated secretion astrocytic proteins involved extracellular matrix cytoskeletal organization increase oxidative stress responses chaperone activity. Several these have identified previous transcriptomic proteomic studies using tissue AD cerebrospinal fluid (CSF). work highlights relevance studying understand pathology potential use as biomarkers for disease. image

Language: Английский

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Development of fluorophores for the detection of oligomeric aggregates of amyloidogenic proteins found in neurodegenerative diseases

Frontiers in Chemistry, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 22, 2023

Alzheimer's disease and Parkinson's are the two most common neurodegenerative diseases globally. These have characteristic late-stage symptoms allowing for differential diagnosis; however, they both share presence of misfolded protein aggregates which appear years before clinical manifestation. Historically, research has focused on detection higher-ordered (or amyloids); recent evidence shown that oligomeric state these plays a greater role in pathology, resulting increased efforts to detect oligomers aid diagnosis. In this review, we summarize some exciting new developments towards development fluorescent probes can amyloidogenic proteins present patients.

Language: Английский

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Long term worsening of amyloid pathology, cerebral function, and cognition after a single inoculation of beta-amyloid seeds with Osaka mutation

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: April 22, 2023

Abstract Alzheimer’s disease (AD) is characterized by intracerebral deposition of abnormal proteinaceous assemblies made amyloid-β (Aß) peptides or tau proteins. These and proteins induce synaptic dysfunctions that are strongly correlated with cognitive decline. Intracerebral infusion well-defined Aβ seeds from non-mutated 1-40 1-42 can increase depositions several months after the infusion. Familial forms AD associated mutations in amyloid precursor protein (APP) production different structures. The Osaka (Aβ osa mutation (E693Δ)) located within sequence thus have structures properties as compared to wt ). Here, we wondered if a single exposure this mutated worsen pathology well downstream events including cognition, cerebral connectivity health inoculation. To answer question inoculated -bearing ) dentate gyrus APP swe /PS1 dE9 mice at age two months. Their cognition were analyzed 4 post-inoculation behavioral evaluation functional MRI. density evaluated histology. impact on was also measured primary cortical neurons. Remarkably, administration induced impairments reduction between brain regions, post-inoculation. It increased plaque oligomers. This first study showing single, sporadic event inoculation fate clinical outcome event. suggests regulates large cascade for long time. Graphical

Language: Английский

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NMDARs in Alzheimer’s Disease: Between Synaptic and Extrasynaptic Membranes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10220 - 10220

Published: Sept. 23, 2024

N-methyl-D-aspartate receptors (NMDARs) are glutamate with key roles in synaptic communication and plasticity. The activation of NMDARs initiates plasticity stimulates cell survival. In contrast, the extrasynaptic can promote death underlying a potential mechanism neurodegeneration occurring Alzheimer's disease (AD). distribution versus has emerged as an important parameter contributing to neuronal dysfunction neurodegenerative diseases including AD. Here, we review concept NMDARs, this population is present numerous membranes but also various non-neuronal cells. Previous evidence regarding membranal NMDRs relation AD mice models brains patients will be reviewed.

Language: Английский

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The intracerebral injection of Aβ1-42 oligomers does not invariably alter seizure susceptibility in mice

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Sept. 7, 2023

Epileptiform activity and seizures are present in patients with Alzheimer's disease (AD) genetic animal models of AD. Amyloid beta 1-42 (Aβ1-42) oligomers thought to be crucial AD can cause neuronal hyperexcitability vitro. However, it is unclear whether these Aβ1-42 the increased seizure susceptibility vivo people models, nor via which mechanisms would do so. We investigated this question by injecting intracerebrally mice assessed its impact on susceptibility.We performed a single intracerebral injection synthetic or scrambled NMRI three different cohorts subjected them an i.v. infusion chemoconvulsant. evoked 1.5 h, 1 week, 3 weeks after oligomers, covering also timepoints locations that were used others similar experimental set-ups.With thioflavine T assay transmission electron microscopy we confirmed monomers spontaneously aggregated oligomers. did not find effect - week their injection.The lack our experiments contrasts recent findings set-ups. Contradicting conclusions frequent they often attributed subtle differences various aggregation forms experiments. presence state-of-the-art methods but cannot ascertain protein aggregates identical those others. Whether previously published best represent role remains unclear.

Language: Английский

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