Evaluating the diagnostic performance of six plasma biomarkers for Alzheimer’s disease and other neurodegenerative dementias in a large Chinese cohort

Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 3, 2025

Abstract Background Ethnic variations and detection methods may lead to differences in diagnostic biomarkers of dementia, few comparative studies have evaluated the six plasma Alzheimer’s disease (AD) other neurodegenerative dementias Chinese population. Methods A cross-sectional cohort 668 participants were enrolled, including 245 amnesic mild cognitive impairment (aMCI) or AD patients with Aβ positive pathology, 67 frontotemporal dementia (FTD), 100 progressive supranuclear palsy (PSP), 72 Lewy bodies (DLB) 184 healthy controls. Additionally, a longitudinal subset 19 aMCI 30 was followed for an average period 1 year. Plasma biomarkers, p-tau181, p-tau217, p-tau231, NfL, GFAP, α-synuclein, simultaneously measured using novel single molecular array method. Aβ42 p-tau181 levels CSF, amyloid PET structural MRI measured. Results p-tau217 p-tau231 most effective diagnosing aMCI/AD (AUC = 0.95 0.93, respectively), while presented best differential diagnosis from PSP, FTD DLB respectively 0.84, 0.81 0.83). α-synuclein as biomarker PSP variant behavior subtypes 0.74, respectively). Among them, GFAP a-synuclein negatively correlated CSF Aβ42/40, positively p-tau181. Besides, associated temporal lobe volume, frontal volume. Longitudinal analysis showed higher could predict decline progression. Conclusions This study validate practicality blood Han population molecule immune Through clinical performance several we found diagnosis, p-tau high accuracy is multiple aspects can reflect dynamic AD.

Язык: Английский

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COVID-19 and the cardiovascular system: a study of pathophysiology and interpopulation variability

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Июнь 7, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans can lead to various degrees of tissue and organ damage, which cardiovascular system diseases are one the main manifestations, such as myocarditis, myocardial infarction, arrhythmia, threaten infected population worldwide. These health populations Although prevalence disease 2019 (COVID-19) has slightly improved with virus mutation vaccination, chronic infection, post-infection sequelae, patients still exist, it is relevant study mechanisms linking COVID-19 (CVD). This article introduces pathophysiological mechanism COVID-19-mediated analyzes recent progress interaction between SARS-CoV-2 from roles angiotensin-converting enzyme (ACE2), cellular molecular mechanisms, endothelial dysfunction, insulin resistance, iron homeostasis imbalance, psychosocial factors, respectively. We also discussed differences involved combined neocoronavirus different provided a theoretical basis for better prevention management.

Язык: Английский

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COVID-19 and Alzheimer’s Disease Share Common Neurological and Ophthalmological Manifestations: A Bidirectional Risk in the Post-Pandemic Future

Cells, Год журнала: 2023, Номер 12(22), С. 2601 - 2601

Опубликована: Ноя. 10, 2023

A growing body of evidence indicates that a neuropathological cross-talk takes place between the coronavirus disease 2019 (COVID-19) -the pandemic severe pneumonia has had tremendous impact on global economy and health since three years after its outbreak in December 2019- Alzheimer’s Disease (AD), leading cause dementia among human beings, reaching 139 million by year 2050. Even though COVID-19 is primary respiratory disease, causative agent, so-called Severe Acute Respiratory Syndrome 2 (SARS-CoV-2), also endowed with high neuro-invasive potential (Neurocovid). The neurological complications COVID-19, resulting from direct viral entry into Central Nervous System (CNS) and/or indirect systemic inflammation dysregulated activation immune response, encompass memory decline anosmia which are typically associated AD symptomatology. In addition, patients diagnosed more vulnerable to SARS-CoV-2 infection inclined clinical outcomes. present review, we better elucidate intimate connection summarizing involved risk factors/targets underlying biological mechanisms shared these two disorders particular focus Angiotensin-Converting Enzyme (ACE2) receptor, APOlipoprotein E (APOE), aging, neuroinflammation cellular pathways Amyloid Precursor Protein (APP)/Amyloid beta (Aβ) tau neuropathologies. Finally, involvement ophthalmological manifestations, including vitreo-retinal abnormalities visual deficits, both discussed. Understanding common physiopathological aspects linking will pave way novel management diagnostic/therapeutic approaches cope them post-pandemic future.

Язык: Английский

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Effect and Mechanism of Rapamycin on Cognitive Deficits in Animal Models of Alzheimer’s Disease: A Systematic Review and Meta-analysis of Preclinical Studies

Journal of Alzheimer s Disease, Год журнала: 2024, Номер 99(1), С. 53 - 84

Опубликована: Апрель 19, 2024

Background: Alzheimer’s disease (AD), the most common form of dementia, remains long-term and challenging to diagnose. Furthermore, there is currently no medication completely cure AD patients. Rapamycin has been clinically demonstrated postpone aging process in mice improve learning memory abilities animal models AD. Therefore, rapamycin potential be significant discovery development drugs for Objective: The main objective this systematic review meta-analysis was investigate effects mechanisms on by examining behavioral indicators pathological features. Methods: Six databases were searched 4,277 articles retrieved. In conclusion, 13 studies included according predefined criteria. Three authors independently judged selected literature methodological quality. Use subgroup analyses explore mechanistic interventions: AD, specific types transgenic models, dosage, periodicity administration. Results: results Morris Water Maze (MWM) test showed that escape latency shortened 15.60 seconds with therapy, indicating ability enhanced mice; number traversed platforms increased 1.53 times, improved significantly corrected deficits. CONCLUSIONS: therapy reduced age-related plaque deposition decreasing AβPP production down-regulating β-secretase γ-secretase activities, furthermore amyloid-β clearance promoting autophagy, as well tau hyperphosphorylation up-regulating insulin-degrading enzyme levels.

Язык: Английский

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ApoE4 causes severe COVID-19 outcomes via downregulation of ACE2

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Сен. 5, 2022

Abstract The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome 2 (SARS-CoV-2); host cell entry this virus relies on the interaction between receptor-binding domain (RBD) of its spike glycoprotein and angiotensin-converting enzyme (ACE2) receptor membranes. In addition to serving as a for SARS-CoV-2, ACE2 was originally discovered protective factor in renin–angiotensin system (RAS) that catalyses degradation angiotensin II (Ang II) Ang 1-7, which involved multiple organ pathology. Recent genetic clinical studies reported ApoE4 expression associated with increased susceptibility SARS-CoV-2 infection development COVID-19, but underlying mechanism currently unclear. present study, using immunofluorescence staining, molecular dynamics simulations, proximity ligation assay (PLA) coimmunoprecipitation (Co-IP) combined biolayer interferometry (BLI) assay, we found ApoE interacts both protein does not show obvious isoform-dependent binding effects. These data suggest increases infectivity manner may depend differential interactions or ACE2. Importantly, further immunoblotting staining results showed significantly downregulates vitro vivo subsequently decreases conversion could worsen tissue lesions; these findings provide possible explain exacerbates COVID-19 disease.

Язык: Английский

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The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 9960 - 9960

Опубликована: Сен. 15, 2024

Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research recent years, especially the context of global COVID-19 pandemic, where its role neurological diseases received widespread attention. ACE2, as multifunctional metalloprotease, not only plays critical cardiovascular system but also an important protection, development, and inflammation regulation nervous system. The pandemic further highlights importance ACE2 SARS-CoV-2 enters host cells by binding to which may directly or indirectly affect system, leading range symptoms. This review aims explore function well potential impact therapeutic various diseases, providing new perspective for treatment disorders.

Язык: Английский

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Human genetic basis of severe or critical illness in COVID-19

Frontiers in Cellular and Infection Microbiology, Год журнала: 2022, Номер 12

Опубликована: Сен. 20, 2022

Coronavirus Disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to considerable morbidity and mortality worldwide. The clinical manifestation of COVID-19 ranges from asymptomatic or mild infection critical illness, such as failure, multi-organ dysfunction even death. Large-scale genetic association studies have indicated that variations affecting SARS-CoV-2 receptors (angiotensin-converting enzymes, transmembrane serine protease-2) immune components (Interferons, Interleukins, Toll-like Human leukocyte antigen) are host determinants related severity COVID-19. Genetic background, 3p21.31 9q34.2 loci were also identified influence outcomes In this review, we aimed summarize current literature focusing on human factors may contribute observed diversified Enhanced understanding viral interactions could provide scientific bases for personalized preventive measures precision medicine strategies.

Язык: Английский

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Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes

Open Biology, Год журнала: 2024, Номер 14(6)

Опубликована: Июнь 1, 2024

Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different via vascular system. We studied impact of apolipoprotein E (APOE) genotype inflammation on infectivity pseudo-typed severe acute syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse human cultured endothelial cells pericytes. Possessing APOE4 allele or having existing systemic enhance severity COVID-19. Using targeted replacement APOE3 mice induced bacterial lipopolysaccharide (LPS), we investigated infection SARS-CoV-2. Here, show that higher murine cerebrovascular pericytes compared cultures expressing APOE4. Furthermore, increasing inflammatory state prior incubation with LPS increased into cells. Our findings provide insights mechanisms underlying infection, highlighting how risk factors such as may exacerbate augmenting virus’s ability infect

Язык: Английский

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Targeted screening of genetic associations with COVID-19 susceptibility and severity

Frontiers in Genetics, Год журнала: 2022, Номер 13

Опубликована: Ноя. 30, 2022

The COVID-19 pandemic has resulted in great morbidity and mortality worldwide human genetic factors have been implicated the susceptibility severity of COVID-19. However, few replicate researches performed, studies on associated genes mainly focused genic regions while regulatory were a lack in-depth dissection. Here, based previously reported variants genes, we designed capture panel covering 1,238 candidate 25 19 targeted-sequenced 96 mild 145 severe patients. Genetic association analysis was conducted between patients, all patients general population, or population. A total 49 confirmed to be with (p < 0.05), corresponding 18 independent loci. Specifically, rs1799964 promoter inflammation-related gene TNF, rs9975538 intron interferon receptor IFNAR2, rs429358 exon APOE, rs1886814 FOXP4-AS1 list widely 3p21.31 ABO confirmed. It is worth noting that, for variants, phenotypes cases controls highly consistent our study previous reports, identified quite different from those suggesting basis SARS-CoV-2 infection might different. Moreover, newly 67 significant 12 11 0.05). Further annotation by RegulomeDB database GTEx eQTL data filtered out two (rs11246060 rs28655829) enhancer broad-spectrum antiviral IFITM3 that affect disease regulating expression. Collectively, novel COVID-19, which provide biological clinical insights into pathogenesis treatment.

Язык: Английский

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Neuroinflammation in Alzheimer’s Disease: A Potential Role of Nose-Picking in Pathogen Entry via the Olfactory System?

Biomolecules, Год журнала: 2023, Номер 13(11), С. 1568 - 1568

Опубликована: Окт. 24, 2023

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide tau deposition, but more recent evidence suggests that neuroinflammation may also play an—at least partial—role in its pathogenesis. In years, emerging research has explored involvement external, invading pathogens starting or accelerating neuroinflammatory processes AD. this narrative review, we advance hypothesis AD be partially caused viral, bacterial, fungal entering brain through nose olfactory system. The system represents plausible route for pathogen entry, given direct anatomical connection early stages We discuss potential mechanisms which exploit pathway initiate neuroinflammation, one them being accidental exposure mucosa hands contaminated with soil feces when picking one’s nose.

Язык: Английский

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