scholarly journals Dynamic changes of CSF sPDGFRβ during ageing and AD progression and associations with CSF ATN biomarkers

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Jun Wang ◽  
Dong-Yu Fan ◽  
Hui-Yun Li ◽  
Chen-Yang He ◽  
Ying-Ying Shen ◽  
...  
Keyword(s):  
Early Stage ◽  
Growth Factor Receptor ◽  
Early Event ◽  
Dynamic Changes ◽  
Brain Capillary ◽  
Normal Ageing ◽  
T Tau ◽  
Phosphorylated Tau 181 ◽  
Normal Status

Abstract Background Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer’s disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. Methods We investigated the dynamic changes of soluble platelet-derived growth factor receptor β (sPDGFRβ) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRβ and ATN biomarkers were analyzed. Results In lifetime, CSF sPDGFRβ continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aβ42 began to decline since the age of 39.6 years, indicating Aβ deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aβ deposition. In AD spectrum, CSF sPDGFRβ was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRβ was positively associated with P-tau181 and T-tau independently of Aβ42, and significantly strengthened the effects of Aβ42 on P-tau181, suggesting that pericyte injury accelerates Aβ-mediated tau hyperphosphorylation. Conclusions Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aβ-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.

scholarly journals Sleep Time Estimated by an Actigraphy Watch Correlates With CSF Tau in Cognitively Unimpaired Elders: The Modulatory Role of APOE

2021 ◽  
Vol 13 ◽  
Author(s):  
Sara López-García ◽  
Carmen Lage ◽  
Ana Pozueta ◽  
María García-Martínez ◽  
Martha Kazimierczak ◽  
...  
Keyword(s):  
Brain Aging ◽  
Amyloid Β ◽  
Sleep Time ◽  
Sleep Monitoring ◽  
Valid Predictor ◽  
Early Biomarker ◽  
T Tau ◽  
The Relationship ◽  
Phosphorylated Tau 181

There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.

scholarly journals Role of androgen receptor expression in early stage ER+/PgR−/HER2– breast cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592095835 ◽  
Author(s):  
Barbara Tagliaferri ◽  
Erica Quaquarini ◽  
Raffaella Palumbo ◽  
Emanuela Balletti ◽  
Daniele Presti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Early Stage ◽  
Tumor Biology ◽  
Growth Factor Receptor ◽  
Primary Objective ◽  
Receptor Expression ◽  
Prognostic Role ◽  
Her2 Breast Cancer

Background: Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR– BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting. Patients and methods: This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR−/Human Epidermal growth factor Receptor 2 (HER2)– BC were included. The primary objective was to analyze the relationship between AR expression and RFS. Results: At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99, p = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR <80% (HR = 0.53, p = 0.008). In addition, breast tumors with higher AR expression had good biological features (low ki67 and nuclear grade) compared with BCs with lower AR expression, at least partly explaining the different outcome. Conclusions: The results of this study support the potential prognostic role of AR in patients with ER+/PgR− BCs and may contribute to the identification of subgroups of high-risk patients.

scholarly journals Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy

2021 ◽  
Vol 13 ◽  
pp. 175883592094941
Author(s):  
Morena Fasano ◽  
Carminia Maria Della Corte ◽  
Giuseppe Viscardi ◽  
Raimondo Di Liello ◽  
Fernando Paragliola ◽  
...  
Keyword(s):  
Head And Neck ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Treatment Options ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Clinical Settings ◽  
Histologic Subtype ◽  
Targeted Agent

Head and neck cancers (HNC) represent the seventh most frequent cancer worldwide, with squamous cell carcinomas as the most frequent histologic subtype. Standard treatment for early stage diseases is represented by single modality surgery or radiotherapy, whereas in the locally advanced and recurrent or metastatic settings a more aggressive multi-modal approach is needed with locoregional intervention and/or systemic therapies. Epidermal Growth Factor Receptor (EGFR) plays an important role in HNC biology and has been studied extensively in preclinical and clinical settings. In this scenario, anti-EGFR targeted agent cetuximab, introduced in clinical practice a decade ago, represents the only approved targeted therapy to date, while the development of immune-checkpoint inhibitors has recently changed the available treatment options. In this review, we focus on the current role of anti-EGFR therapies in HNCs, underlying available clinical data and mechanisms of resistance, and highlight future perspectives regarding their role in the era of immunotherapy.

Can trust become a factor of economic growth? Dynamic changes in the level of trust of Russian youth

2020 ◽  
pp. 92-107 ◽  
Author(s):  
A. I. Bakhtigaraeva ◽  
A. A. Stavinskaya
Keyword(s):  
Institutional Environment ◽  
Negative Effects ◽  
Dynamic Changes ◽  
Generalized Trust ◽  
Level Of Education ◽  
Advantages And Disadvantages ◽  
The Future ◽  
Analysis Of Dynamics

The article considers the role of trust in the economy, the mechanisms of its accumulation and the possibility of using it as one of the growth factors in the future. The advantages and disadvantages of measuring the level of generalized trust using two alternative questions — about trusting people in general and trusting strangers — are analyzed. The results of the analysis of dynamics of the level of generalized trust among Russian youth, obtained within the study of the Institute for National Projects in 10 regions of Russia, are presented. It is shown that there are no significant changes in trust in people in general during the study at university. At the same time, the level of trust in strangers falls, which can negatively affect the level of trust in the country as a whole, and as a result have negative effects on the development of the economy in the future. Possible causes of the observed trends and the role of universities are discussed. Also the question about the connection between the level of education and generalized trust in countries with different quality of the institutional environment is raised.

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

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