A5039811171- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Cholinesterase and Neurodegenerative Diseases
- Dementia and Cognitive Impairment Research
- Computational Drug Discovery Methods
- Intracerebral and Subarachnoid Hemorrhage Research
- Trace Elements in Health
- Bioinformatics and Genomic Networks
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Genetics and Neurodevelopmental Disorders
- Olfactory and Sensory Function Studies
- Liver Disease Diagnosis and Treatment
- Alcoholism and Thiamine Deficiency
- Neuroinflammation and Neurodegeneration Mechanisms
- Cerebrovascular and genetic disorders
- Parkinson's Disease Mechanisms and Treatments
- Hops Chemistry and Applications
- Medicinal Plants and Bioactive Compounds
- Neurological Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Extracellular vesicles in disease
- Endoplasmic Reticulum Stress and Disease
- Amino Acid Enzymes and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
Fondazione IRCCS Istituto Neurologico Carlo Besta
2015-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2012
Mario Negri Institute for Pharmacological Research
2009
beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673-->valine-673 (A673V)] that causes only in the homozygous state, whereas heterozygous carriers were unaffected, consistent a recessive Mendelian trait of inheritance. The A673V affected processing, resulting enhanced beta-amyloid (Abeta) production and formation amyloid fibrils vitro. Co-incubation mutated wild-type peptides conferred...
Prions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of misfolded prion protein (PrPSc). The unique mechanism transmission and appearance a variant form Creutzfeldt–Jakob disease, which has been linked to consumption prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that disease prions circulate in body fluids from people whom is silently incubating.
Atypical neuropathological and molecular phenotypes of bovine spongiform encephalopathy (BSE) have recently been identified in different countries. One these phenotypes, named "amyloidotic" (BASE), differs from classical BSE for the occurrence a distinct type disease-associated prion protein (PrP), termed PrPSc, presence PrP amyloid plaques. Here, we show that agents responsible BASE possess biological properties upon transmission to transgenic mice expressing inbred lines nontransgenic...
Serpins represent the most broadly distributed superfamily of proteases inhibitors. They contribute to a variety physiological functions and any alteration serpin-protease equilibrium can lead severe consequences. SERPINA3 dysregulation has been associated with Alzheimer's disease (AD) prion diseases. In this study, we investigated differential expression serpin members in neurodegenerative SERPIN was analyzed human frontal cortex samples from cases sporadic Creutzfeldt-Jakob (sCJD),...
Tau is a microtubule-associated protein that promotes assembly and stabilization of cytoskeleton microtubules. It mostly expressed in neuronal glial cells but it also present non-neural such as fibroblasts lymphocytes. An altered tau produces pathology resulting neurodegenerative diseases Alzheimer's disease tauopathies. has been suggested to be multifunctional protein, due its localization different cellular compartments. However further functions are still unclear. We analyzed the...
Abstract Protein misfolding and aggregation is a central feature of several neurodegenerative disorders including Alzheimer’s disease (AD), in which assemblies amyloid β (Aβ) peptides accumulate the brain form parenchymal and/or vascular amyloid. A widely accepted concept that AD characterized by distinct clinical neuropathological phenotypes. Recent studies revealed Aβ might have structural differences among brains such pleomorphic can correlate with We found both sporadic inherited forms...
One of the earliest pathological features characterizing Alzheimer's disease (AD) is loss dendritic spines. Among many factors potentially mediating this neuronal connectivity, contribution Rho-GTPases particular interest. This family proteins has been known for years as a key regulator actin cytoskeleton remodeling. More recent insights have indicated how its complex signaling might be triggered also in conditions. Here, we showed that Rho-GTPase member Rac1 levels decreased frontal cortex...
Alzheimer’s disease (AD), frontotemporal dementia (FTD), and with Lewy bodies (DLB) are the three major neurodegenerative dementias. In this study, we provide evidence that an alteration in extracellular vesicles (EVs) release is common across most dementias, AD, DLB, FTD. Specifically, analyzed plasma EVs groups of patients affected by FTD, found a significant reduction concentration larger size all patient groups. We then investigated whether loss neurotrophic factors also pathogenic...
Abstract Cerebral amyloid angiopathy (CAA) is a small vessel disease, causing spontaneous intracerebral hemorrhage (ICH) in the elderly. It strongly associated with Alzheimer disease (AD), as most CAA patients show deposition of Aβ—i.e. basic component parenchymal deposits—in cerebral vessels. Iatrogenic early-onset has been recently identified history traumatic brain injury or other well extra-cerebral lesions that led to neurosurgery medical procedures intravascular embolization by...
The approval of new disease-modifying therapies by the U.S. Food and Drug Administration European Medicine Agency makes it necessary to optimize non-invasive cost-effective tools for identification subjects at-risk developing Alzheimer's Disease (AD). Plasma biomarkers are excellent candidates. However, their ability reflect cerebrospinal fluid (CSF) profile - that remains date gold standard biochemical diagnosis AD needs be confirmed validated before implementation in clinical practice....
Abstract Background In recent years, the seed amplification assay (SAA) has enabled identification of pathological TDP-43 in cerebrospinal fluid (CSF) and olfactory mucosa (OM) patients with genetic forms frontotemporal dementia (FTD) amyotrophic lateral sclerosis (ALS). Here, we investigated seeding activity OM samples collected from sporadic ALS. Methods were (a) motor neuron diseases (MND), including spinal ALS ( n = 35), bulbar 18), primary 10), facial onset sensory neuronopathy 2); (b)...
Although Alzheimer's disease (AD) is usually sporadic, in a small proportion of cases it familial and can be linked to mutations β-amyloid precursor protein (APP). Unlike the other genetic defects, mutation [alanine-673→valine-673] (A673V) causes only homozygous condition with enhanced amyloid β (Aβ) production aggregation; heterozygous carriers remain unaffected. It not clear how misfolding aggregation Aβ affected vivo by this whether correlates its toxic effects. No animal models...
Abstract We developed a novel therapeutic strategy for Alzheimer’s disease (AD) exploiting the properties of natural variant Amyloid-β (Aβ) carrying A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Aβ, hindering conformational changes and assembly thereof. As prototypic compound we designed six-mer mutated peptide (Aβ1-6 ), linked HIV-related TAT protein, is widely used brain delivery cell membrane penetration drugs. The resulting...
Prion diseases are neurodegenerative disorders which caused by an accumulation of the abnormal, misfolded prion protein known as scrapie (PrPSc). These unique they occur sporadic, genetic and acquired forms. Sporadic Creutzfeldt-Jakob Disease (CJD) is most common human disease, accounting for approximately 85–90% cases, whereas autosomal dominant forms, due to mutations in gene (PRNP), account 10–15% cases. Genetic forms show a striking variability their clinical neuropathological picture...
Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and frontotemporal (FTD) represent the three major neurodegenerative dementias characterized by abnormal brain protein accumulation. In this study, we investigated extracellular vesicles (EVs) neurotrophic factors in cerebrospinal fluid (CSF) of 120 subjects: 36 AD, 30 DLB, 34 FTD 20 controls. Specifically, CSF EVs were analyzed Nanoparticle Tracking Analysis measured ELISA. We found higher EV concentration lower size AD DLB groups...
Abstract Alzheimer’s disease (AD), the leading cause of dementia in older adults, is a double proteinopathy characterized by amyloid-β (Aβ) and tau pathology. Despite enormous efforts that have been spent last decades to find effective therapies, late pharmacological interventions along course disease, inaccurate clinical methodologies enrollment patients, inadequate biomarkers for evaluating drug efficacy not allowed development an therapeutic strategy. The approaches followed so far...
The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those typical BSE, resulting in clinically and pathologically distinct phenotype. Whether peripheral tissues BASE-affected cattle contain infectivity unknown. This critical issue since the readily transmissible to variety hosts including primates, suggesting that humans may be susceptible. We carried out bioassays transgenic mice overexpressing PrP...
Alzheimer’s disease (AD) is the most common form of dementia. It’s a chronic and untreatable neurodegenerative with irreversible progression has important social economic implications in terms direct medical care costs. Despite prolonged expensive efforts employed by scientific community over last few decades, no effective treatments are still available for patients, development disease-modifying drugs now really urgent need. The recent failure clinical trials based on immunotherapeutic...
Abstract Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that affects millions of people worldwide. AD pathogenesis intricate. It primarily involves two main molecular players—amyloid-β (Aβ) and tau—which actually have intrinsic trend to generate assemblies are toxic neurons. Incomplete knowledge the mechanisms inducing onset sustaining progression disease, as well lack valid models fully recapitulate human until now hampered development a successful therapy for AD....