Alejandra Sekler

University of Chile, CiudadSantiago, Santiago, Chile

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Publications (3)4.16 Total impact

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    ABSTRACT: During the last few years, an increasing amount of evidence points to the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration. Central nervous system inflammation is a process associated with several neurodegenerative disorders, including Alzheimer’s disease (AD). Many hypotheses have been postulated to explain the pathogenesis of AD. Recent findings point to amyloid-β (Aβ) oligomers as responsible for synaptic impairment in neuronal degeneration, but amyloid abnormalities are among major factors affecting the function and survival of neuronal cells. The tau protein hypothesis has been developed and refined based on the fact that tau hyperphosphorylation and self-aggregation constitutes a common feature of most of the altered signaling pathways in AD. Known mediators of inflammation have been found in plaques, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Additional evidence for the involvement of inflammation in AD is provided by epidemiological data and retrospective clinical data showing positive effects of nonsteroidal anti-inflammatory drugs. Cytokines and trophic factors produced by glial cells can trigger anomalous hyperphosphorylation of tau. Glial production of these mediators indicates that innate immunity is involved in AD. Thus, a neuroimmunological approach to AD becomes relevant. In this context, endogenous danger signals such as altered lipoproteins and oxidized lipids appear to affect glial cells, inducing release of such mediators. Indeed, when alterations of cholesterol metabolism occur, the neurochemical events of oxidative stress, Aβ peptide, and tau protein seem to represent a set of physiological mechanisms to respond to impaired brain cholesterol dynamics. All these mechanisms, for example, changes in neuroimmunomodulation, dislipidemias, cholesterol abnormalities, and other metabolic alterations, appear to be interrelated. To date, there are no specific diagnostic tools for AD that allow early treatment, thus improving quality of life for AD patients and reducing the morbidity and mortality associated with the late complications. Therefore, a search for innovative molecular markers for early diagnosis of AD is essential. Here we discuss the molecular aspects of the role of neuroinflammation and cholesterol in AD and some perspectives toward molecular early diagnosis.
    12/2008: pages 125-137;
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    ABSTRACT: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP), plasma malondialdehyde and total antioxidative capacity (TAC), as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59) and a control group of neurologically normal subjects (n = 29), attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery), while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol) of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC) of patients. In this context, the subset of subjects exhibiting cognitive impairment were divided into two subgroups according with their Global Dementia Scale performance: a subgroup with mild AD and a subgroup with moderate to severe AD. Significant differences in AOC were found between subgroups. The different correlations between cognitive impairment of subgroups of subjects with the oxidative stress profile are discussed in the context of AD pathogenesis.
    Neuropsychiatric Disease and Treatment 09/2008; 4(4):715-22. · 2.00 Impact Factor
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    ABSTRACT: The objective of this study was to obtain normative data for naming and semantic memory (SM) tests in the elderly Spanish population. A total of 121 Spanish-speaking senior citizens were assessed with the Boston Naming Test (BNT). Of these, 79 were assessed with the Semantic Fluency Test (Sem-Flu) and 72 with the Pyramids and Palm Trees Test (PPT). Mean scores were 49.6 (SD = 5.6) for the BNT, 49.6 (SD = 2.2) for the PPT, and 16.9 (SD = 4.9) for the Sem-Flu. All SM tests were significantly influenced by participants' level of education (p < .01). The BNT was also significantly influenced by gender. A significant positive association was found between naming and SM tests (p < .01). Normative data for naming and SM tests could be useful in clinical assessment and research in Spanish-speaking dementia patients.
    Journal of Clinical and Experimental Neuropsychology 01/2008; 30(1):1-6. · 2.16 Impact Factor