Relationship Between Balance and Cognitive Performance in Older People

We investigated the relationship between balance and cognitive level in a group of 70 women with no definite Alzheimer’s disease or mild cognitive impairment diagnosis and no impairment of daily activity. Static stabilometry and the Montreal Cognitive Assessment (MoCA) test were performed. The antero-posterior sway component was demonstrated to be the best predictor of the MoCA overall score. As visual and proprioceptive components of balance could safely be excluded in our assessments, the vestibular system is to be considered as a putative link between balance and cognitive impairment

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

The Unexpected Role of A\u3b21-42 Monomers in the Pathogenesis of Alzheimer's Disease

Amyloid- (A) has been proposed as a biomarker and a drug target for the therapy of Alzheimer\u2019s disease (AD). The neurotoxic entity and relevance of each conformational form of A to AD pathology is still under debate; A oligomers are considered the major killer form of the peptide whereas monomers have been proposed to be involved in physiological process. Here we reviewed some different effects mediated by monomers and oligomers on mechanisms involved in AD pathogenesis such as autophagy and tau aggregation. Data reported in this review demonstrate that A monomers could have a major role in sustaining the pathogenesis of AD and that AD therapy should be focused not only in the removal of oligomers but also of monomers

Alternative, Non-secretase Processing of Alzheimer's β-Amyloid Precursor Protein during Apoptosis by Caspase-6 and -8

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Although the pathogenesis of AD is unknown, it is widely accepted that AD is caused by extracellular accumulation of a neurotoxic peptide, known as Abeta. Mutations in the beta-amyloid precursor protein (APP), from which Abeta arises by proteolysis, are associated with some forms of familial AD (FAD) and result in increased Abeta production. Two other FAD genes, presenilin-1 and -2, have also been shown to regulate Abeta production; however, studies examining the biological role of these FAD genes suggest an alternative theory for the pathogenesis of AD. In fact, all three genes have been shown to regulate programmed cell death, hinting at the possibility that dysregulation of apoptosis plays a primary role in causing neuronal loss in AD. In an attempt to reconcile these two hypotheses, we investigated APP processing during apoptosis and found that APP is processed by the cell death proteases caspase-6 and -8. APP is cleaved by caspases in the intracellular portion of the protein, in a site distinct from those processed by secretases. Moreover, it represents a general effect of apoptosis, because it occurs during cell death induced by several stimuli both in T cells and in neuronal cells

Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study

The circadian rhythm hypothesis of bipolar disorder (BD) suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute) or II cases of bipolar depression

The role of oxidative stress in the pathogenesis of Alzheimer's disease

[ES]: La presencia de estrés oxidativo es la característica más temprana de la Enfermedad de Alzheimer (EA), lo cual proporciona un atractivo objetivo para intervenciones terapéuticas. Entre los mayores retos que se presentan actualmente están el establecimiento de la fuente de estrés oxidativo y la determinación de cómo este proceso puede influir en la etiología de la Enfermedad de Alzheimer. Este es un tema complejo, pues varios procesos, enzimáticos y no-enzimáticos, están implicados en la formación de oxígeno reactivo y otras moléculas tóxicas. En este artículo discutimos el progreso en el entendimiento de estos procesos[EN]: Oxidative stress is the earliest feature of Alzheimer disease and an attractive therapeutic target. One of the major challenges today is to establish the source of the reactive oxygen and to determine the role of oxidative stress in the etiology of Alzheimer disease. This is a complex issue since a variety of enzymatic and non-enzymatic processes are involved in the formation of reactive oxygen and other toxic molecules. In this review, we discuss progress in the understanding of these processes.Peer reviewe

The Decrease of Uch-L1 Activity Is a Common Mechanism Responsible for Aβ 42 Accumulation in Alzheimer’s and Vascular Disease

Alzheimer’s disease (AD) is a multifactorial pathology causing common brain spectrum disorders in affected patients. These mixed neurological disorders not only include structural AD brain changes but also cerebrovascular lesions. The main aim of the present issue is to find the factors shared by the two pathologies. The decrease of ubiquitin C-terminal hydrolase L1 (Uch-L1), a major neuronal enzyme involved in the elimination of misfolded proteins, was observed in ischemic injury as well as in AD, but its role in the pathogenesis of AD is far to be clear. In this study we demonstrated that Uch-L1 inhibition induces BACE1 up-regulation and increases neuronal and apoptotic cell death in control as well as in transgenic AD mouse model subjected to Bengal Rose, a light-sensitive dye inducing that induces a cortical infarction through photo-activation. Under the same conditions we also found a significant activation of NF-κB. Thus, the restoration of Uch-L1 was able to completely prevent both the increase in BACE1 protein levels and the amount of cell death. Our data suggest that the Uch-L1-mediated BACE1 up-regulation could be an important mechanism responsible for Aβ peptides accumulation in vascular injury and indicate that the modulation of the activity of this enzyme could provide new therapeutic strategies in AD