A5041508320- Prion Diseases and Protein Misfolding
- Olfactory and Sensory Function Studies
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Trace Elements in Health
- Amino Acid Enzymes and Metabolism
- Infectious Encephalopathies and Encephalitis
- Alcoholism and Thiamine Deficiency
- 14-3-3 protein interactions
- Viral Infections and Immunology Research
- Amyotrophic Lateral Sclerosis Research
- Peripheral Neuropathies and Disorders
- Multiple Sclerosis Research Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Peroxisome Proliferator-Activated Receptors
- Bacteriophages and microbial interactions
- Botulinum Toxin and Related Neurological Disorders
- Microbial metabolism and enzyme function
- S100 Proteins and Annexins
- Cardiomyopathy and Myosin Studies
- Cancer, Hypoxia, and Metabolism
- Intracranial Aneurysms: Treatment and Complications
- Biochemical Analysis and Sensing Techniques
- Folate and B Vitamins Research
University of Verona
2013-2023
University of California, San Francisco
2016
Sapienza University of Rome
2009
Humanitas University
2006
University of Milan
2006
Istituti di Ricovero e Cura a Carattere Scientifico
2006
Ospedale Maggiore
2006
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2006
Definite diagnosis of sporadic Creutzfeldt–Jakob disease in living patients remains a challenge. A test that detects the specific marker for disease, prion protein (PrPCJD), by means real-time quaking-induced conversion (RT-QuIC) testing cerebrospinal fluid has sensitivity 80 to 90% disease. We have assessed accuracy RT-QuIC analysis nasal brushings from olfactory epithelium diagnosing patients.
Early and accurate in vivo diagnosis of Creutzfeldt-Jakob disease (CJD) is necessary for quickly distinguishing treatable from untreatable rapidly progressive dementias future therapeutic trials. This early becoming possible using the real-time quaking-induced conversion (RT-QuIC) seeding assay, which detects minute amounts disease-specific pathologic prion protein cerebrospinal fluid (CSF) or olfactory mucosa (OM) samples.To develop an algorithm CJD by RT-QuIC assay on CSF samples, OM...
Isolated REM sleep behaviour disorder (RBD) is an early-stage α-synucleinopathy in most, if not all, affected subjects. Detection of pathological α-synuclein peripheral tissues patients with isolated RBD may identify those progressing to Parkinson's disease, dementia Lewy bodies or multiple system atrophy, the ultimate goal testing preventive therapies. Real-time quaking-induced conversion (RT-QuIC) provided evidence seeding activity CSF and olfactory mucosa α-synucleinopathies. The aim this...
We applied RT-QuIC assay to detect α-synuclein aggregates in cerebrospinal fluid (CSF) of patients with suspected Creutzfeldt-Jakob disease who had a neuropathological diagnosis dementia Lewy bodies (DLB) (n = 7), other neurodegenerative diseases mixed pathology 20), or without Lewy-related 49). The test sensitivity 92.9% and specificity 95.9% distinguishing α-synucleinopathies from non-α-synucleinopathies. When performed the CSF DLB 36), was positive 17/20 probable DLB, 0/6 possible 0/10...
In patients with suspected dementia Lewy bodies, the detection of disease-associated α-synuclein in easily accessible tissues amenable to be collected using minimally invasive procedures remains a major diagnostic challenge. This approach has potential take advantage modern molecular assays for diagnosis α-synucleinopathy and, turn, optimize recruitment and selection clinical trials, drugs directed at counteracting aggregation. this study, we explored accuracy real-time quaking-induced...
Olfactory cortexes and the olfactory tracts are involved in sporadic Creutzfeldt–Jakob disease. We examined peripheral regions of sensory pathway, including mucosa, to assess whether pathologic infectious prion protein (PrPSc) is deposited epithelium lining nasal cavity.
The disease phenotype of bovine spongiform encephalopathy (BSE) and the molecular/ biological properties its prion strain, including host range characteristics BSE-related disorders, have been extensively studied since discovery in 1986. In recent years, systematic testing brains cattle coming to slaughter resulted identification at least two atypical forms BSE. These emerging disorders are characterized by novel conformers pathological protein (PrP(TSE)), named high-type (BSE-H) low-type...
Abstract Real‐Time Quaking‐Induced Conversion ( RT ‐Qu IC ) testing of human cerebrospinal fluid CSF is highly sensitive and specific in discriminating sporadic CJD patients from those without prion disease. Here, using samples 113 64 non‐prion disease patients, we provide the first direct concurrent comparison our improved assay to previous assay, which similar commonly used internationally for diagnosis. This extended demonstrated a ~21% increase diagnostic sensitivity, 2‐day reduction...
The early and accurate in vivo diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is essential order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive clinical include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity the cerebrospinal fluid (CSF) or other tissues. total CSF tau concentration has also been used a setting for...
In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate other α-synucleinopathies. It unknown whether these variable results might be related to a different distribution α-syn OM. Thus, we investigated nasal swab (NS) performed areas coverage by neuroepithelium, such agger nasi (AN) and middle turbinate (MT), affect the α-syn.NS was 66 PD 29 non-PD between September...
In prion diseases, the cellular protein (PrP(C)) is converted to an insoluble and protease-resistant abnormal isoform termed PrP(Sc). different strains, PrP(Sc) shows distinct sites of endogenous or exogenous proteolysis generating a core fragment named PrP27-30. Sporadic Creutzfeldt-Jakob disease (sCJD), most frequent human disease, clinically presents with variety neurological signs. As yet, clinical variability observed in sCJD has not been fully explained by molecular studies relating...
A novel neuronal tauopathy, mainly confined to hypothalamus and brainstem tegmentum, has recently been reported in patients with autoantibodies the cell-adhesion molecule IgLON5. We describe a patient anti-IgLON5 syndrome, who presented dysautonomia sleep disorder, followed by subacute dementia. Postmortem brain examination disclosed tau pathology prevailing hippocampus, amygdala, locus coeruleus, addition microglial/neuronal TDP-43 pathology, overexpression of aberrantly phosphorylated...
Abstract Objective Real‐time quaking‐induced conversion (RT‐QuIC) assays detect prion‐seeding activity in a variety of human biospecimens, including cerebrospinal fluid and olfactory mucosa swabs. The assay has shown high diagnostic accuracy patients with prion disorders. Recently, advances these tests have led to markedly improved sensitivity reduced times. Accordingly, an algorithm been proposed that entails the use RT‐QuIC analysis both sample types diagnose sporadic Creutzfeldt‐Jakob...
Abstract Objective The detection of prion seeding activity in CSF and olfactory mucosal brushings using real‐time quaking‐induced conversion assays allows highly accurate clinical diagnosis sporadic Creutzfeldt–Jakob disease. To gauge transmission risks associated with these biospecimens their testing, we have bioassayed infectivity levels patients’ brain tissue, nasal brushings, CSF, assessed the pathogenicity amplified products seeded disease prions. Methods We obtained from patients a...
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% all cases. Current criteria intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), positive 14-3-3-protein assay in cerebrospinal fluid (CSF). In sCJD, phenotype may vary, depending upon genotype codon 129 protein gene (PRNP), site common methionine/valine polymorphism, two conformers pathological protein. Based...
Abstract INTRODUCTION We assessed TAR DNA‐binding protein 43 (TDP‐43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration TDP‐43‐immunoreactive pathology (FTLD‐TDP) by TDP‐43 amplification assay (TDP43‐SAA) immunocytochemical analysis. METHODS The TDP43‐SAA was optimized using frontal cortex samples from 16 post mortem cases FTLD‐TDP, FTLD tau inclusions, controls. Subsequently, were collected 17 15 healthy controls, three carrying...
In multiple sclerosis (MS) autonomic cardiovascular dysfunction is an uncommon, but potentially dangerous event, to which studies of spectral analysis heart rate variability have not been applied, yet. Material and methods – We studied 16 patients with definite MS (11 women 5 men, mean age 30.3 ± 7.4 yrs., EDSS 2.06±1.42) sex- age-matched healthy controls. Besides reflex tests (valsalva manoeuvre, deep breathing, lying standing, Blood Pressure response standing sustained handgrip), each...
To identify predictors of short- and long-term outcomes in acute myelitis (AM).First episodes AM were retrospectively identified a single institution. Information regarding demographics, clinical status, laboratory workup, magnetic resonance imaging the spine brain, electrophysiological assessment was collected. Tau, 14-3-3 protein, cystatin C levels assessed de novo stored cerebrospinal fluid samples.A neurological department database. Patients Fifty-three patients with first episode AM.The...
In 2007, we reported a patient with an atypical form of Creutzfeldt-Jakob disease (CJD) heterozygous for methionine-valine (MV) at codon 129 who showed novel pathological prion protein (PrPTSE) conformation glycoform (AG) profile and intraneuronal PrP deposition. the present study, further characterize conformational properties this (PrPTSE MVAG), showing that PrPTSE MVAG is composed multiple conformers biochemical distinct from those type 1 2 MV sporadic CJD (sCJD). Experimental...
<h3>Objective</h3> To describe a novel molecular and pathological phenotype of Creutzfeldt-Jakob disease. <h3>Patient</h3> A 69-year-old woman with behavioral personality changes followed by rapidly evolving dementia. <h3>Results</h3> Postmortem examination the brain showed intracellular prion protein deposition axonal swellings filled amyloid fibrils. Biochemical analysis disclosed previously unrecognized PrP<sup>Sc</sup>tertiary structure lacking diglycosylated species. Genetic revealed...
Differential proteomic analysis has been performed on the cerebrospinal fluid (CSF) of six healthy and patients suffering form sporadic Creutzfeldt-Jakob disease (sCJD), age- sex-matched, after immuno-subtraction albumin immunoglobulins. These maps have revealed 28 polypeptide chains differentially modulated in sCJD samples, which 10 appeared to be up-regulated, remaining 18 being down-regulated. Among those, 13 could identified upon digestion MALDI-TOF, MS analysis. In addition, strong...
Rapidly progressive dementia (RPD) is a rare presentation of different neurological disorders characterized by cognitive impairment leading to loss functional independence within 24 months or less. The increasing recognition treatable non-prion causes RPD has made the differential diagnosis with sporadic Creutzfeldt-Jakob disease (sCJD) crucial importance. We therefore assessed frequency etiologies and evaluated accuracy newly proposed diagnostic criteria for sCJD. Clinical records patients...