A5084526781- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Neonatal and fetal brain pathology
- Neuroscience and Neuropharmacology Research
- Neonatal Respiratory Health Research
- Intracerebral and Subarachnoid Hemorrhage Research
- Nicotinic Acetylcholine Receptors Study
- Neuroscience of respiration and sleep
- Neurogenesis and neuroplasticity mechanisms
- Diabetes Treatment and Management
- Dementia and Cognitive Impairment Research
- Neurological Disorders and Treatments
- Natural Antidiabetic Agents Studies
- Neurotransmitter Receptor Influence on Behavior
- Regulation of Appetite and Obesity
- Computational Drug Discovery Methods
- Histone Deacetylase Inhibitors Research
- Advanced Glycation End Products research
- Memory and Neural Mechanisms
- Tryptophan and brain disorders
- Metabolism, Diabetes, and Cancer
- Axon Guidance and Neuronal Signaling
- S100 Proteins and Annexins
Biomedical Research and Innovation Institute of Cadiz
2017-2024
Universidad de Cádiz
2015-2024
Instituto de Investigación Biomédica de A Coruña
2017-2023
Massachusetts General Hospital
2005-2013
Harvard University
2004-2013
Alzheimer’s Research UK
2013
Charles River Associates
2013
Indiana University School of Medicine
2013
Universidad de Navarra
2002-2008
Harvard University Press
2006-2008
Synapse loss correlates with a cognitive decline in Alzheimer's disease (AD), but whether this is caused by fibrillar deposits known as senile plaques or soluble oligomeric forms of amyloid beta (Abeta) controversial. By using array tomography, technique that combines ultrathin sectioning tissue immunofluorescence, allowing precise quantification small structures, such synapses, we have tested the hypothesis Abeta surrounding contributes to synapse mouse model AD. We find are surrounded halo...
Abstract Alzheimer’s disease (AD) is characterized by senile plaques and neurodegeneration although the neurotoxic mechanisms have not been completely elucidated. It clear that both oxidative stress inflammation play an important role in illness. The compound curcumin, with a broad spectrum of anti‐oxidant, anti‐inflammatory, anti‐fibrilogenic activities may represent promising approach for preventing or treating AD. Curcumin small fluorescent binds to amyloid deposits. In present work we...
Abstract Mitochondria contribute to shape intraneuronal Ca 2+ signals. Excessive taken up by mitochondria could lead cell death. Amyloid beta (Aβ) causes cytosolic overload, but the effects of Aβ on mitochondrial levels in Alzheimer’s disease (AD) remain unclear. Using a ratiometric indicator targeted neuronal and intravital multiphoton microscopy, we find increased associated with plaque deposition death transgenic mouse model cerebral β-amyloidosis. Naturally secreted soluble applied onto...
The Tg2576 transgenic mouse model of human cerebral amyloid angiopathy is characterized by age-dependent cerebrovascular deposition amyloid-beta (Abeta) starting from 9 months age and progressively worsening to involve most pial arterioles 18 months; soluble Abeta levels are elevated long before vascular takes place in this model. It has been suggested that alone sufficient impair blood flow (CBF) regulation thereby contributing the early progression Alzheimer's disease. Using laser speckle...
Previous clinical studies have documented a close relationship between cerebrovascular disease and risk of Alzheimer's disease. We examined possible mechanistic interactions through use experimental stroke models in transgenic mouse model β-amyloid deposition (APPswe/PS1dE9). Following middle cerebral artery occlusion, we observed rapid increase amyloid plaque burden the region surrounding infarction. In human tissue samples, however, were unable to detect localized adjacent infarcts. To...
Aggregation of amyloid-β (Aβ) peptide in the brain form neuritic plaques and cerebral amyloid angiopathy (CAA) is a key feature Alzheimer's disease (AD). Microglial cells surround aggregated Aβ are believed to play role AD pathogenesis. A therapy for that has entered clinical trials administration anti-Aβ antibodies. One mechanism by which certain antibodies have been proposed exert their effects via antibody-mediated microglial activation. Whether, when, or what extent activation occurs...
Abstract Background Both Alzheimer’s disease (AD) and type 2 diabetes (T2D) share common pathological features including inflammation, insulin signaling alterations, or vascular damage. AD has no successful treatment, the close relationship between both diseases supports study of antidiabetic drugs to limit slow down brain pathology in AD. Empagliflozin (EMP) is a sodium-glucose co-transporter inhibitor, newest class agents. EMP controls hyperglycemia reduces cardiovascular comorbidities...
Although extensive evidence supports the role of β-amyloid (Aβ) in Alzheimer disease (AD), neurotoxic mechanisms underlying AD pathogenesis are not understood. On other hand, neuronal loss is pathologic feature that best correlates with cognitive impairment. We hypothesized cholinergic neurodegeneration may lead to Aβ deposition and tested this by inducing selective lesions APPswe/PS1dE9 mice murine p75 saporin (mu p75-SAP). Intracerebroventricular removed approximately 50% innervation...
Abstract Alzheimer's disease is characterized by the presence of aggregates amyloid beta (Aβ) in senile plaques and tau neurofibrillary tangles, as well marked neuron synapse loss. Of these pathological changes, loss correlates most strongly with cognitive decline. Synapse occurs prominently around due to accumulations oligomeric Aβ. Recent evidence suggests that may also play a role but interactions Aβ remain be determined. In this study, we generated novel transgenic mouse line, APP / PS...
Type 2 diabetes (T2D) is an important risk factor to suffer dementia, including Alzheimer's disease (AD), and some neuropathological features observed in dementia could be mediated by T2D metabolic alterations. Since brain atrophy impaired neurogenesis have been both AD we analyzed central nervous system (CNS) morphological alterations the db/db mice (leptin receptor KO mice), as a model of long-term insulin resistance T2D, C57Bl6 fed with high fat diet (HFD), induced prediabetes. Db/db...
Type 2 diabetes (T2D) mellitus and Alzheimer's disease (AD) are two prevalent diseases with comparable pathophysiological features genetic predisposition. Patients AD more susceptible to develop T2D. However, the molecular mechanism linking T2D remains elusive. In this study, we have generated a new mouse model test hypothesis that would prompt onset of in mice. To our hypothesis, crossed Alzheimer APPswe/PS1dE9 (APP/PS1) transgenic mice partially deficient leptin signaling (db/+). Body...
Abstract The involvement of the cholinergic system in learning and memory together with cognitive enhancing properties 5‐HT 6 receptor antagonists led us to study relationship between receptors neurotransmission. A selective lesion, induced by injection immunotoxin 192‐IgG‐Saporin into nucleus basalis magnocellularis, failed alter density mRNA or protein expression deafferentated frontal cortex, suggesting that are not located on neurons. antagonist SB‐357134 (0.001–1 µ m ) a...
Alzheimer disease (AD) is characterized both by senile plaques and neurodegeneration, although the details of relationship between 2 are not well understood. We postulated that oxidative stress resulting from may mediate plaques' effects on local neuronal processes. Using multiphoton microscopy, we directly demonstrate generation reactive oxygen species plaques. After screening several natural antioxidants ex vivo, assessed in vivo effect orally administered APPswe/PS1d9 transgenic mice....
Abstract Imaging of cerebrovascular β‐amyloid (cerebral amyloid angiopathy) is complicated by the nearly universal overlap this pathology with Alzheimer's pathology. We performed positron emission tomographic imaging Pittsburgh Compound B on 42‐year‐old man early manifestations Iowa‐type hereditary cerebral angiopathy, a form disorder little or no plaque deposits fibrillar β‐amyloid. The results demonstrated increased retention selectively in occipital cortex, sparing regions typically...