Salivary GFAP as a potential biomarker for diagnosis of mild cognitive impairment and Alzheimer's disease and its correlation with neuroinflammation and apoptosis

Katsipis, Georgios; Tzekaki, Elena E.; Tsolaki, Magda; Pantazaki, Αnastasia A.

doi:10.1016/j.jneuroim.2021.577744

Cited by 25 publications

(20 citation statements)

References 99 publications

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“…Astrocyte reactivity or astrogliosis is a pathological process in AD that is commonly found in the vicinity of brain Aβ plaques in AD patients. − Glial fibrillary acidic protein (GFAP) is the main constituent of the astrocytic cytoskeleton, regarded as a hallmark of inflammation due to its overexpression during reactive astrogliosis. , To determine the effects of chiral liposomes on glial activation and inflammation, immunohistochemical staining for GFAP was performed in the hippocampus and cerebral cortex of APP/PS1 mice. Figure shows the alterations of GFAP immunostaining in the brains of mice after chiral liposome treatment.…”

Section: Resultsmentioning

confidence: 99%

Aspartic Acid-Modified Phospholipids Regulate Cell Response and Rescue Memory Deficits in APP/PS1 Transgenic Mice

Wang

Gao

Qian

et al. 2022

ACS Chem. Neurosci.

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Misfolding and accumulation of amyloid-β (Aβ) to form senile plaques are the main neuropathological signatures of Alzheimer’s disease (AD). Decreasing Aβ production, inhibiting Aβ aggregation, and clearing Aβ plaques are thus considered an important strategy for AD treatment. However, numerous drugs cannot enter the AD clinical trials due to unsatisfactory biocompatibility, poor blood–brain barrier penetration, little biomarker impact, and/or low therapeutic indicators. Here, a pair of chiral aspartic acid-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (l- and d-Asp-DPPE) are prepared to build stabilized chiral liposomes. We find that both l- and d-liposomes are able to rescue Aβ aggregation-induced apoptosis, oxidative stress, and calcium homeostasis, in which the effect of d-liposomes is more obvious than that of l-ones. Furthermore, in AD model mice (APPswe/PS1d9 double-transgenic mice), chiral liposomes not only show biosafety but also strongly improve cognitive deficits and reduce Aβ deposition in the brain. Our results suggest that chiral liposomes, particularly, d-liposomes, could be a potential therapeutic approach for AD treatment. This study opens new horizons by showing that liposomes will be used for drug development in addition to delivery and targeting functions.

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Section: Resultsmentioning

confidence: 99%

Aspartic Acid-Modified Phospholipids Regulate Cell Response and Rescue Memory Deficits in APP/PS1 Transgenic Mice

Wang

Gao

Qian

et al. 2022

ACS Chem. Neurosci.

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“…Glial fibrillar acidic protein (GFAP) is a component of the cytoskeleton of astrocytes, which plays an important role in modulating neuronal inflammation (Yang and Wang, 2015). According to the study of Katsipis et al (2021) two different immunological assays, namely ELISA and Dot Blot, were applied to detect GFAP levels in the saliva of participants in the experiment. The results obtained by both methods showed a decrease in GFAP levels in patients with AD or MCI compared to healthy subjects.…”

Section: Unique Biomarkers Mirna Biomarkers Referencesmentioning

confidence: 99%

“…In addition, GFAP levels in the saliva of AD patients are significantly lower than those of MCI patients. The possible reason for this was that GFAP were susceptible to several post-transcriptional modifications, which would hinder their transfer from the brain to the saliva and reduce their solubility (Katsipis et al, 2021). Since salivary GFAP can be used to differentiate between healthy individuals, people suffering from MCI, and AD patients, it may present as a reliable biomarker for the screen of the neurological status of people.…”

Section: Unique Biomarkers Mirna Biomarkers Referencesmentioning

confidence: 99%

Is liquid biopsy mature enough for the diagnosis of Alzheimer’s disease?

Gong

Zhang

Liu

et al. 2022

Front. Aging Neurosci.

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The preclinical diagnosis and clinical practice for Alzheimer’s disease (AD) based on liquid biopsy have made great progress in recent years. As liquid biopsy is a fast, low-cost, and easy way to get the phase of AD, continual efforts from intense multidisciplinary studies have been made to move the research tools to routine clinical diagnostics. On one hand, technological breakthroughs have brought new detection methods to the outputs of liquid biopsy to stratify AD cases, resulting in higher accuracy and efficiency of diagnosis. On the other hand, diversiform biofluid biomarkers derived from cerebrospinal fluid (CSF), blood, urine, Saliva, and exosome were screened out and biologically verified. As a result, more detailed knowledge about the molecular pathogenesis of AD was discovered and elucidated. However, to date, how to weigh the reports derived from liquid biopsy for preclinical AD diagnosis is an ongoing question. In this review, we briefly introduce liquid biopsy and the role it plays in research and clinical practice. Then, we summarize the established fluid-based assays of the current state for AD diagnostic such as ELISA, single-molecule array (Simoa), Immunoprecipitation–Mass Spectrometry (IP–MS), liquid chromatography–MS, immunomagnetic reduction (IMR), multimer detection system (MDS). In addition, we give an updated list of fluid biomarkers in the AD research field. Lastly, the current outstanding challenges and the feasibility to use a stand-alone biomarker in the joint diagnostic strategy are discussed.

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“…The analysis of isolated astrocyte-derived exosomes (ADE) GLAST positive from plasma of AD patients and controls showed significantly higher levels of the cytokines IL-6, TNF-α, and IL-1β and of numerous complement proteins ( Goetzl et al, 2018 ). Surprisingly, GFAP is also described as a potential biomarker for early AD in the saliva of MCI and AD patients where its levels are correlated with Aβ 42 , IL-1β, and caspase-8 ( Katsipis et al, 2021 ). An increase of GFAP staining is commonly observed in the parenchyma of AD cases ( Serrano-Pozo et al, 2013 ).…”

Section: Breaking Bad: When Do Astrocytes Become Toxic To Surrounding...mentioning

confidence: 99%

The Multifaceted Neurotoxicity of Astrocytes in Ageing and Age-Related Neurodegenerative Diseases: A Translational Perspective

et al. 2022

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In a healthy physiological context, astrocytes are multitasking cells contributing to central nervous system (CNS) homeostasis, defense, and immunity. In cell culture or rodent models of age-related neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), numerous studies have shown that astrocytes can adopt neurotoxic phenotypes that could enhance disease progression. Chronic inflammatory responses, oxidative stress, unbalanced phagocytosis, or alteration of their core physiological roles are the main manifestations of their detrimental states. However, if astrocytes are directly involved in brain deterioration by exerting neurotoxic functions in patients with NDDs is still controversial. The large spectrum of NDDs, with often overlapping pathologies, and the technical challenges associated with the study of human brain samples complexify the analysis of astrocyte involvement in specific neurodegenerative cascades. With this review, we aim to provide a translational overview about the multi-facets of astrocyte neurotoxicity ranging from in vitro findings over mouse and human cell-based studies to rodent NDDs research and finally evidence from patient-related research. We also discuss the role of ageing in astrocytes encompassing changes in physiology and response to pathologic stimuli and how this may prime detrimental responses in NDDs. To conclude, we discuss how potentially therapeutic strategies could be adopted to alleviate or reverse astrocytic toxicity and their potential to impact neurodegeneration and dementia progression in patients.

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Salivary GFAP as a potential biomarker for diagnosis of mild cognitive impairment and Alzheimer's disease and its correlation with neuroinflammation and apoptosis

Cited by 25 publications

References 99 publications

Aspartic Acid-Modified Phospholipids Regulate Cell Response and Rescue Memory Deficits in APP/PS1 Transgenic Mice

Aspartic Acid-Modified Phospholipids Regulate Cell Response and Rescue Memory Deficits in APP/PS1 Transgenic Mice

Is liquid biopsy mature enough for the diagnosis of Alzheimer’s disease?

The Multifaceted Neurotoxicity of Astrocytes in Ageing and Age-Related Neurodegenerative Diseases: A Translational Perspective

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