Oxidative Stress Mediates the Pathogenic Effect of Different Alzheimer's Disease Risk Factors

Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. Mechanistically, the major cause of the disease bases on the altered processing of the amyloid-β (Aβ) precursor protein (APP), resulting in the accumulation and aggregation of neurotoxic forms of Aβ. Aβ derives from the sequential proteolytic cleavage of the β- and γ-secretases on APP. The causes of Aβ accumulation in the common sporadic form of AD are not completely known, but they are likely to include oxidative stress (OS). OS and Aβ are linked to each other since Aβ aggregation induces OS in vivo and in vitro, and oxidant agents increase the production of Aβ. Moreover, OS produces several effects that may contribute to synaptic function and cell death in AD. We and others have shown that the expression and activity of β-secretase (named BACE1; β-site APP cleaving enzyme) is increased by oxidant agents and by lipid peroxidation product 4-hydroxynonenal and that there is a significant correlation between BACE1 activity and oxidative markers in sporadic AD. OS results from several cellular insults such as aging, hyperglycemia, hypoxic insults that are all well known risk factors for AD development. Thus, our data strengthen the hypothesis that OS is a basic common pathway of Aβ accumulation, common to different AD risk factors

Transgenic Expression of the Amyloid-β Precursor Protein-Intracellular Domain Does Not Induce Alzheimer's Disease–Like Traits In Vivo

BACKGROUND: Regulated intramembranous proteolysis of the amyloid-beta precursor protein by the gamma-secretase yields amyloid-beta, which is the major component of the amyloid plaques found in Alzheimer's disease (AD), and the APP intracellular domain (AID). In vitro studies have involved AID in apoptosis and gene transcription. In vivo studies, which utilize transgenic mice expressing AID in the forebrain, only support a role for AID in apoptosis but not gene transcription. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have further characterized several lines of AID transgenic mice by crossing them with human Tau-bearing mice, to determine whether over-expression of AID in the forebrain provokes AD-like pathologic features in this background. We have found no evidence that AID overexpression induces AD-like characteristics, such as activation of GSK-3beta, hyperphosphorylation of Tau and formation of neurofibrillary pathology. CONCLUSIONS/SIGNIFICANCE: Overall, these data suggest that AID transgenic mice do not represent a model that reproduces the overt biochemical and anatomo-pathologic lesions observed in AD patients. They can still be a valuable tool to understand the role of AID in enhancing the cell sensitivity to apoptotic stimuli, whose pathways still need to be characterized

The Fate of Political Scientists in Europe. From Myth to Action

This open access book offers a systematic survey of the attitudes and values of European political scientists. It builds a structural interpretation based on empirical data, as well as offering reflections on the future structure of the discipline. In the middle of a delicate phase of changes marked by the effects of pandemic and the war in Ukraine, we need to pay attention to the factors that are affecting not only the ‘objects’ of Political Science as a discipline but also its interactions with the world around it. First, this book asks to what extent the work of European political scientists is impacted by the current change. Second, their attitudes and predisposition about the future goals of the discipline are analysed. In the final chapter, the authors seek to understand to what extent a diffuse but still not completely institutionalized academic discipline will be able to produce a comprehensive impact around the European society, in order to be more visible and effective in policy making and policy processes

Looking for eclecticism? structural and contextual factors underlying political science's relevance gap: Evidence from the Italian case

The article deals with the perception of political science's limited social relevance, by proposing a theoretical framework of analysis through which the Italian case is addressed. Thus, we assume that the prevailing nature of the discipline (variously defined as soft/pure/divergent/rural) results in specific patterns of behaviour which strongly constrain political science's capacity to increase the importance of its social role. This framework is adopted to analyse, using original empirical data, the Italian case where notwithstanding the institutionalisation of the subject within university curricula, and the relatively promising level of internationalisation of research, the 'political' and 'social' roles of political science continue to be of a substantially limited entity. Furthermore, three professional pathways emerge as prevailing (pure public scholar, pure academic, pure public intellectual) and largely independent of each other, thus emphasising the problems of the visibility and relevance of the subject. Consequently, in order to fill the social relevance gap, we discuss the need for a fourth, more eclectic professional pathway

Nemo pfofita in patria: Trudnyi put' italianskoi politicheskoi nauki k obshestvennomu vliyaniu

The paper aims to discuss the current public image of political science in a country with a strong tradition in political discourse , where the empirical study of politics has been present since the end of XIX century if not longer , when the Italian elitist school paved the way for a new direction political science . Over the past two decades, political scientists have had the chance to reverse their scarse visibility, and have clearly attempted to take advantage of the new demand for change from within Italian society, by trying to achieve greater visibility outside the ac ademic community and to play a stronger role in public debate. What our analysis reveals is that, notwithstanding the institutionalization of the subject with in university curricula , and the relative ly promising level of internationalisation of research, t he \u201cpolitical\u201d and \u201csocial\u201d role s of Italian political s cience continue to be of a substantially limited entit

Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use

Alzheimer’s disease (AD) is the most common type of dementia, affecting more than 5 million Americans, with steadily increasing mortality and incredible socio-economic burden. Not only have therapeutic efforts so far failed to reach significant efficacy, but the real pathogenesis of the disease is still obscure. The current theories are based on pathological findings of amyloid plaques and tau neurofibrillary tangles that accumulate in the brain parenchyma of affected patients. These findings have defined, together with the extensive neurodegeneration, the diagnostic criteria of the disease. The ability to detect changes in the levels of amyloid and tau in cerebrospinal fluid (CSF) first, and more recently in blood, has allowed us to use these biomarkers for the specific in-vivo diagnosis of AD in humans. Furthermore, other pathological elements of AD, such as the loss of neurons, inflammation and metabolic derangement, have translated to the definition of other CSF and blood biomarkers, which are not specific of the disease but, when combined with amyloid and tau, correlate with the progression from mild cognitive impairment to AD dementia, or identify patients who will develop AD pathology. In this review, we discuss the role of current and hypothetical biomarkers of Alzheimer’s disease, their specificity, and the caveats of current high-sensitivity platforms for their peripheral detection