Your search for: 'author:("Maccioni, Ricardo B.")' has returned 25 results. (0.012s) Save search

Authors: Cortés, Nicole | Andrade, Víctor | Maccioni, Ricardo B.

Article Type: Review Article

Abstract: Alzheimer‘s disease (AD) is the most frequent type of dementia in the elderly, severely affecting functional and executive skills of subjects suffering from this disease. Moreover, the distress of caregivers as well as the social implications constitute a critical issue for families. Furthermore, cognitive impairment, along with behavioral disorders and neuropsychiatric symptoms are characteristics of AD. Although these are present with variations in prevalence, intensity, and progression, an important core of them is visible before cognitive impairment, especially depression and apathy, which affect at least 50% of patients. The most updated literature shows that depression and/or behavioral and neuropsychiatric symptoms …(BNS) are part of the initial phase of the disease rather than just a risk factor. Thus, mood disorders are associated with anomalies in specific brain regions that disturb the normal balance of neurotransmission. This in turn is linked with an inflammatory pathway that leads to microglial activation and aggregated neurofibrillary tangle formation, finally triggering neuronal loss, according to our neuroimmunomodulation theory. Altogether, inflammation and tau aggregation are observed in preclinical stages, preceding the BNS of patients, which in turn are exhibited earlier than cognitive and functional impairment detected in AD. This review is focused on the latest insights of cellular and molecular processes associated with BNS in asymptomatic early-onset stages of AD. An important medical research focus is to improve quality of life of patients, through prevention and treatments of AD, and the study of behavioral disorders and early event in AD pathogenesis has a major impact. Show more

Keywords: Alzheimer’s disease, apathy, asymptomatic stages, behavioral disorders, neuroimmunomodulation, neuroinflammation, neuropsychiatric symptoms

DOI: 10.3233/JAD-180005

Citation: Journal of Alzheimer's Disease, vol. 63, no. 3, pp. 899-910, 2018

Authors: Morales, Inelia | Jiménez, José M. | Mancilla, Marcela | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Neuroinflammation is a process related to the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Increasing sets of evidence support the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration, a process we are calling neuroimmunomodulation in AD. On the basis of the hypothesis that pathological tau aggregates induce microglial activation with the subsequent events of the neuroinflammatory cascade, we have studied the effects of tau oligomeric species and filamentous structures over microglial cells in vitro. Tau oligomers and fibrils were induced by arachidonic acid and then their actions …assayed upon addition to microglial cells. We showed activation of the microglia, with significant morphological alterations as analyzed by immunofluorescence. The augmentation of nitrites and the proinflammatory cytokine IL-6 was evaluated in ELISA assays. Furthermore, conditioned media of stimulated microglia cells were exposed to hippocampal neurons generating altered patterns in these cells, including shortening of neuritic processes and cytoskeleton reorganization. Show more

Keywords: Alzheimer's disease, glial cells, neuroinflammation, tau aggregates

DOI: 10.3233/JAD-131843

Citation: Journal of Alzheimer's Disease, vol. 37, no. 4, pp. 849-856, 2013

Authors: Farías, Gonzalo | Pérez, Patricio | Slachevsky, Andrea | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Platelets are major reservoirs of circulating amyloid-β and amyloid-β protein precursor (AβPP) and have been postulated as a reliable source for biological markers of Alzheimer's disease (AD). We have recently demonstrated that tau is also present in platelets, and that there are differences in the electrophoretic patterns of platelet tau forms in AD subjects with respect to controls. Here, we demonstrate that modifications in platelet tau forms occur independently of age in a broad population of 104 neurologically healthy individuals. More interesting, a strong correlation of platelet markers with the degree of cognitive impairment was evidenced in a group of …47 AD patients in comparison with 19 cognitive healthy subjects. In our series, platelet tau forms ratio had a sensitivity of 75.7% and specificity of 73.7%, respectively. We also found that platelet tau displays a significantly higher correlation with the presence of AD than the analyses of platelet AβPP. Show more

Keywords: Alzheimer's disease, cognitive impairment, human platelets, tau biomarker

DOI: 10.3233/JAD-2012-120304

Citation: Journal of Alzheimer's Disease, vol. 31, no. 1, pp. 65-69, 2012

Authors: Hernandez, Paula | Lee, Gloria | Sjoberg, Marcela | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is characterized by the accumulation of protein filaments, namely extracellular amyloid-β (Aβ) fibrils and intracellular neurofibrillary tangles, which are composed of aggregated hyperphosphorylated tau. Tau hyperphosphorylation is the product of deregulated Ser/Thr kinases such as cdk5 and GSK3β. In addition, tau hyperphosphorylation also occurs at Tyr residues. To find a link between Aβ and tau phosphorylation, we investigated the effects of short-term Aβ treatments on SHSY-5Y cells. We analyzed phosphorylated tau variants in lipid rafts and the possible role of Tyr18 and Ser396/404 tau phosphorylation in Aβ-induced signaling cascades. After 2 min of Aβ treatment, phospho-Tyr18-tau and …its association with rafts increased. Phospho-Ser 396/404-tau became detectable in rafts after 10 min treatment, which temporally correlated with the detection of cdk5 and p35 activator in lipid rafts. To determine the role of cdk5 in tau phosphorylation at Ser396/404 in lipid rafts, we pre-incubated cells with cdk5 inhibitor roscovitine, and observed that the Aβ-induced tau phosphorylation at Ser 396/404 in rafts was abolished as well as cdk5/p35 association with rafts. These data suggest a role for cdk5 in the Aβ-promoted early events involving tau hyperphosphorylation, and their possible implications for AD pathogenesis. Show more

Keywords: Alzheimer's disease, amyloid-β, cdk5, Fyn, lipid rafts, neuronal membrane, tau phosphorylation

DOI: 10.3233/JAD-2009-0933

Citation: Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 149-156, 2009

Authors: González, Andrea | Guzmán-Martínez, Leonardo | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Background: A major drawback in Alzheimer’s disease (AD) is the lack of validated biomarkers for routine clinical diagnostic. We have reported earlier a novel blood biomarker, named Alz-tau® , based on variants of platelet tau. This marker evaluates the ratio of high molecular weight tau (HMWtau) and the low molecular weight (LMWtau) tau. Objective: To analyze a potential novel source of antigen for Alz-tau® , plasma tau, detected by immunoreactivity with the novel monoclonal antibody, tau51. Methods: We evaluated tau variants in plasma precipitated with ammonium sulfate from 36 AD patients and 15 control subjects by western blot with this …novel monoclonal antibody. Results: The HMW/LMWtau ratio was statistically different between AD patients and controls. Conclusions: Plasma tau variants are suitable to be considered as a novel antigen source for the Alz-tau® biomarker for AD. Show more

Keywords: Alz-tau®, Alzheimer’s disease, HMW/LMWtau ratio, monoclonal antibodies, peripheral biomarkers, tau protein in the human plasma

DOI: 10.3233/JAD-200386

Citation: Journal of Alzheimer's Disease, vol. 77, no. 2, pp. 877-883, 2020

Authors: Morales, Inelia | Cerda-Troncoso, Cristóbal | Andrade, Víctor | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a progressive cognitive impairment of patients, affecting around 12% of people older than 65 years old. WHO estimated that over 48.6 million all over the world suffer this disease. On the basis of cumulative results on our research, we have postulated the neuroimmunomodulation hypothesis that appears to provide a reasonable explanation of both the preclinical and clinical observations. In this context, the long-term activation of the innate immune system triggers an anomalous cascade of molecular signals, finally leading to tau oligomerization in the pathway to neuronal degeneration. In the present scenario …of the failure of many anti-AD drugs, nutraceutical compounds provide an avenue for AD prevention and possibly as coadjuvants in the treatment of this disease. Recent discoveries point to the relevance of curcumin, a natural anti-inflammatory agent, in controlling oxidative stress and improving cholinergic function in the brain, even though the mechanisms underlying these actions are unknown. We investigated the effects of curcumin in cultures of neuronal cells. For this study, we exposed cells to prooxidant conditions, both in the presence and absence of curcumin. Our data reveal that curcumin exert a strong neuroprotective effect in N2a cells, thus preventing toxicity by oxidative agents H2 O2 and Fe+3 . This is supported by results that indicate that curcumin control the neurodegenerative effects of both oxidative agents, relieving cells from the loss of neuritogenic processes induced by prooxidants. In addition, curcumin was able to slow down the tau aggregation curve and disassemble tau pathological oligomeric structures. Data suggest that curcumin could be a potential compound for prevention of cognitive disorders associated with AD. Show more

Keywords: Alzheimer’s disease, curcumin and derivatives, functional effects in neurons, prevention, treatment

DOI: 10.3233/JAD-170354

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 451-460, 2017

Authors: Farías, Gonzalo A. | Guzmán-Martínez, Leonardo | Delgado, Carolina | Maccioni, Ricardo B.

Article Type: Review Article

Abstract: Alzheimer's disease is a growing health problem worldwide. The pharmaceutical industry has not recently developed any new drugs that have had a significant impact on the natural history of the disease, so considerable attention has been given to nutraceuticals and nutritional bioactive compounds that can be obtained directly from diet or supplementation. These compounds may be able to modify physiopathological processes responsible for neurodegeneration and/or to have pro-cognitive properties. Here, we review current knowledge on the role of diet modifications, lipid and carbohydrates consumption, vitamin supplementation, and the possible effects of antioxidant and nutraceutical compounds with neuroprotective activity, in the …prevention and treatment of Alzheimer's disease and related disorders. Show more

Keywords: Alzheimer's disease, antioxidants, clinical trials, food supplements, nutraceuticals, vitamins

DOI: 10.3233/JAD-132741

Citation: Journal of Alzheimer's Disease, vol. 42, no. 2, pp. 357-367, 2014

Authors: Fernández, Jorge A. | Rojo, Leonel | Kuljis, Rodrigo O. | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Virtually none of the hypotheses on Alzheimer's disease (AD) pathogenesis address the earliest events that trigger the molecular alterations that precede cerebral degeneration and account for the diversity of risk factors that converge on a well-defined disease phenotype. We propose that long-term activation of the innate immune system by an individual array of risk factors constitutes a unifying mechanism leading to the triggering of an inflammatory cascade that converges in cytoskeletal alterations (tau aggregation, paired helical filament formation) as a previously hypothesized final common pathway in AD. The key pathogenic phenomena consist in the long-term, maladaptive activation of innate immunity-triggering …receptors – such as the toll-like and advanced glycation end-products receptors, and others located in the microglial membrane – by seemingly heterogeneous risk factors such as hyperlipidemia, hyperglycemia, oxidative stress, head injury, amyloid oligomers, etc. Our hypothesis provides a unifying mechanism that explains both the diversity of risk factors acting over long periods of time and the individual response to such insults. This formulation is amenable to both empirical testing and implementation into therapeutic strategies that may lead to effective prevention of AD as well as other disorders in which impaired regulation of the innate immunity is the unifying cause of the condition. Show more

Keywords: Alzheimer's disease, danger signals, glial cells, inflamatory cascades, innate immunity, neuronal cells, tau protein

DOI: 10.3233/JAD-2008-14307

Citation: Journal of Alzheimer's Disease, vol. 14, no. 3, pp. 329-333, 2008

Authors: Lavados, Manuel | Guillón, Marta | Mujica, María Cristina | Rojo, Leonel E. | Fuentes, Patricio | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Oxidative stress constitutes a hallmark of Alzheimer's disease (AD). Recent studies also point to redox active metals such as iron, copper and zinc in mediating oxidative stress in AD pathogenesis. However, the reactivity of cerebrospinal fluid (CSF) iron and its possible correlation with the severity of cognitive decline in both Alzheimer's patients and subjects with mild cognitive impairment (MCI) is still unknown. Here we show that different stages of cognitive and functional impairment are associated with changes in CSF reactive iron. In this work, we compared CSF samples from {56} elders, classified into 4 groups according to their scores on …the Clinical Dementia Rating scale (CDR). Total CSF iron was analyzed by atomic absorption spectrometry. Redox-active iron was analyzed by a novel fluorimetric assay. One-way ANOVA was used to test differences in mean values, and Newman-Keuls Multiple Comparison Test was used for multi group comparisons. No difference in total CSF iron was found between different groups. Significant amounts of redox-active iron were found in CSF and their levels correlated with the extent of cognitive impairment. Redox-active CSF iron levels increased with the degree of cognitive impairment from normal to MCI subjects, while AD patients showed an abrupt decrease to levels close to zero. Given the relevance of oxidative damage in neurodegeneration, it might be possible to associate the development of cognitive and functional decline with the presence of redox-active iron in the CSF. The decrease in redox-active iron found in AD patients may represent a terminal situation, whereby the central nervous system attempts to minimize iron-associated toxicity. Show more

Keywords: Alzheimer disease, cerebrospinal fluid, iron, oxidative stress

DOI: 10.3233/JAD-2008-13211

Citation: Journal of Alzheimer's Disease, vol. 13, no. 2, pp. 225-232, 2008

Authors: Neumann, Karen | Farías, Gonzalo | Slachevsky, Andrea | Perez, Patricio | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Platelets are a major peripheral reservoir of the amyloid-β protein precursor, so they have been considered as a potential biological marker of Alzheimer's disease (AD). Here, it is demonstrated that tau protein is also present in platelets and that the levels of oligomeric species of this protein could serve as a novel and reliable biological marker for AD. Blood samples were obtained from 15 AD patients and 10 paired-age controls and platelets were separated via differential centrifugation. The purity of platelets was determined by flow cytometry and microscopy and the presence of tau was determined by immunofluorescence and immunoblots with …tau specific antibodies. Immunofuorescence and immunoblot patterns of platelets were positive for tau. Immunoblots also showed the presence of high molecular weight (HMW) variants of tau that appeared to correspond to oligomeric forms of the protein. The ratio of HMW tau respect to tau monomeric species was significantly higher in AD patients than controls. The present is the first description of the presence of tau in platelets. The analysis of different tau fractions in platelets could serve as a new biological marker for AD. Show more

Keywords: Alzheimer's disease, cognitive impairment, human platelets, molecular biomarkers, protein self aggregation, tau proteins

DOI: 10.3233/JAD-2011-101641

Citation: Journal of Alzheimer's Disease, vol. 25, no. 1, pp. 103-109, 2011