16 results on '"Zecca, Chiara"'
Search Results
2. Sarcopenia screening in elderly with Alzheimer’s disease: performances of the SARC-F-3 and MSRA-5 questionnaires
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Bramato, Giulia, Barone, Roberta, Barulli, Maria Rosaria, Zecca, Chiara, Tortelli, Rosanna, Filardi, Marco, and Logroscino, Giancarlo
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- 2022
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3. Irisin Levels in Cerebrospinal Fluid Correlate with Biomarkers and Clinical Dementia Scores in Alzheimer Disease.
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Dicarlo, Manuela, Pignataro, Patrizia, Zecca, Chiara, Dell'Abate, Maria Teresa, Urso, Daniele, Gnoni, Valentina, Giugno, Alessia, Borlizzi, Francesco, Zerlotin, Roberta, Oranger, Angela, Colaianni, Graziana, Colucci, Silvia, Logroscino, Giancarlo, and Grano, Maria
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IRISIN ,CEREBROSPINAL fluid ,ALZHEIMER'S disease ,TAU proteins ,DEMENTIA ,MILD cognitive impairment - Abstract
Objective: Irisin, released by muscles during exercise, was recently identified as a neuroprotective factor in mouse models of Alzheimer disease (AD). In a cohort of AD patients, we studied cerebrospinal fluid (CSF) and plasma irisin levels, sex interactions, and correlations with disease biomarkers. Methods: Correlations between CSF and plasma irisin levels and AD biomarkers (amyloid β 1‐42, hyperphosphorylated tau, and total tau [t‐tau]) and Clinical Dementia Rating Scale Sum of Boxes (CDR‐SOB) were analyzed in a cohort of patients with Alzheimer dementia (n = 82), mild cognitive impairment (n = 44), and subjective memory complaint (n = 20) biologically characterized according to the recent amyloid/tau/neurodegeneration classification. Results: CSF irisin was reduced in Alzheimer dementia patients (p < 0.0001), with lower levels in female patients. Moreover, CSF irisin correlated positively with Aβ42 in both female (r = 0.379, p < 0.001) and male (r = 0.262, p < 0.05) patients, and negatively with CDR‐SOB (r = −0.234, p < 0.05) only in female patients. A negative trend was also observed between CSF irisin and t‐tau levels in all patients (r = −0.144, p = 0.082) and in the female subgroup (r = −0.189, p = 0.084). Interpretation: The results highlight the relationship between irisin and biomarkers of AD pathology, especially in females. Our findings also offer perspectives toward the use of irisin as a marker of the AD continuum. ANN NEUROL 2024;96:61–73 [ABSTRACT FROM AUTHOR]
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- 2024
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4. Narcissistic Personality Disorder as Prodromal Feature of Early-Onset, GRN-Positive bvFTD: A Case Report.
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Michelutti, Marco, Urso, Daniele, Gnoni, Valentina, Giugno, Alessia, Zecca, Chiara, Vilella, Davide, Accadia, Maria, Barone, Roberta, Dell'Abate, Maria Teresa, De Blasi, Roberto, Manganotti, Paolo, and Logroscino, Giancarlo
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NARCISSISTIC personality disorder ,DELAYED diagnosis ,FRONTOTEMPORAL dementia ,MENTAL illness ,MAGNETIC resonance imaging ,FRONTOTEMPORAL lobar degeneration - Abstract
Background: Behavioral variant frontotemporal dementia (bvFTD) typically involves subtle changes in personality that can delay a timely diagnosis. Objective: Here, we report the case of a patient diagnosed of GRN-positive bvFTD at the age of 52 presenting with a 7-year history of narcissistic personality disorder, accordingly to DSM-5 criteria. Methods: The patient was referred to neurological and neuropsychological examination. She underwent 3 Tesla magnetic resonance imaging (MRI) and genetic studies. Results: The neuropsychological examination revealed profound deficits in all cognitive domains and 3T brain MRI showed marked fronto-temporal atrophy. A mutation in the GRN gene further confirmed the diagnosis. Conclusions: The present case documents an unusual onset of bvFTD and highlights the problematic nature of the differential diagnosis between prodromal psychiatric features of the disease and primary psychiatric disorders. Early recognition and diagnosis of bvFTD can lead to appropriate management and support for patients and their families. This case highlights the importance of considering neurodegenerative diseases, such as bvFTD, in the differential diagnosis of psychiatric disorders, especially when exacerbations of behavioral traits manifest in adults. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia.
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Malerba, Francesca, Florio, Rita, Arisi, Ivan, Zecca, Chiara, Dell'Abate, Maria Teresa, Logroscino, Giancarlo, and Cattaneo, Antonino
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CEREBROSPINAL fluid examination ,BIOMARKERS ,KRUSKAL-Wallis Test ,ALZHEIMER'S disease ,TAUOPATHIES ,MANN Whitney U Test ,FISHER exact test ,DEMENTIA patients ,COMPARATIVE studies ,IMMUNOASSAY ,RESEARCH funding ,DESCRIPTIVE statistics ,FRONTOTEMPORAL dementia ,NEURODEGENERATION - Abstract
Introduction: Frontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs. Methods: By the means of a new immunoassay, we have measured and analyzed the proNGF levels in 43 cerebrospinal fluids (CSF) from FTD patients, and compared the results to those obtained in CSF from 84 Alzheimer's disease (AD), 15 subjective memory complaints (SMC) and 13 control subjects. Results: A statistically significant difference between proNGF levels in FTD compared to AD, SMC and controls subjects was found. The statistical models reveal that proNGF determination increases the accuracy of FTD diagnosis, if added to the clinically validated CSF biomarkers. Discussion: These results suggest that proNGF could be included in a panel of biomarkers to improve the FTD diagnosis. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Survival in Incident Cases with Frontotemporal Lobar Degeneration: A Registry-Based Study.
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Borroni, Barbara, Urso, Daniele, Zecca, Chiara, Binetti, Giuliano, Fostinelli, Silvia, Benussi, Luisa, Ghidoni, Roberta, Tarantino, Barbara, Rivolta, Jasmine, Dell'Abate, Maria Teresa, Alberici, Antonella, and Logroscino, Giancarlo
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FRONTOTEMPORAL lobar degeneration ,ALZHEIMER'S disease ,SURVIVAL rate ,DISEASE duration ,FRONTOTEMPORAL dementia - Abstract
Population-based registries represent a unique sample to estimate survival. The aim of the present study was to assess survival rates and predictors of outcome in incidental frontotemporal lobar degeneration (FTLD). Incident cases with FTLD, included between January 1, 2017 to December 31, 2017, have been followed for five years. Median survival was 8.16 years from disease onset and 5.38 years from diagnosis. Survival rates did not differ between phenotypes. Shorter disease duration from onset to diagnosis was associated with poorer outcome (p = 0.01). FTLD is a relatively homogeneous disease in terms of survival. Future multinational population-based studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. The Relationship Between Muscle Strength and Cognitive Performance Across Alzheimer's Disease Clinical Continuum.
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Filardi, Marco, Barone, Roberta, Bramato, Giulia, Nigro, Salvatore, Tafuri, Benedetta, Frisullo, Maria Elisa, Zecca, Chiara, Tortelli, Rosanna, and Logroscino, Giancarlo
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ALZHEIMER'S disease ,MUSCLE strength ,COGNITIVE ability ,EXPLICIT memory ,MILD cognitive impairment ,NEUROPSYCHOLOGICAL tests - Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive cognitive decline, mostly prominent in the domain of memory, but also associated with other cognitive deficits and non-cognitive symptoms. Reduced muscle strength is common in AD. However, the current understanding of its relationship with cognitive decline is limited. This study investigates the relationship between muscle strength and cognition in patients with AD and mild cognitive impairment (MCI). We enrolled 148 consecutive subjects, including 74 patients with probable AD dementia, 37 MCI, and 37 controls. Participants underwent neuropsychological evaluation focused on attention, working memory, declarative memory and learning. Muscle strength and muscle mass were measured through hand dynamometer and bio-electrical impedance analysis, respectively. Patients with AD dementia were divided with respect to the severity of cognitive impairment into mild and moderate-to-severe patients. Moderate-to-severe patients with AD presented lower handgrip strength than MCI and controls. No differences were observed in muscle mass. In MCI and AD dementia, handgrip strength was associated with overall cognitive functioning, attentional and memory performance. The routine implementation of handgrip strength assessment in the clinical work-up of patients with MCI and AD could potentially represent a simple method to monitor functional and cognitive decline along the disease course. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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8. proNGF Measurement in Cerebrospinal Fluid Samples of a Large Cohort of Living Patients With Alzheimer's Disease by a New Automated Immunoassay.
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Malerba, Francesca, Arisi, Ivan, Florio, Rita, Zecca, Chiara, Dell'Abate, Maria Teresa, Bruni Ercole, Bruno, Camerini, Serena, Casella, Marialuisa, Logroscino, Giancarlo, and Cattaneo, Antonino
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ALZHEIMER'S patients ,CEREBROSPINAL fluid ,IMMUNOASSAY ,BIOMARKERS ,ALZHEIMER'S disease - Abstract
The discovery of new biomarkers for Alzheimer's disease (AD) is essential for an accurate diagnosis, to conceive new strategies of treatments, and for monitoring the efficacy of potential disease-modifying therapies in clinical trials. proNGF levels in the cerebrospinal fluid (CSF) represent a promising diagnostic biomarker for AD, but its validation was hampered by the absence of a reliable immunoassay. In the literature, proNGF is currently measured in postmortem brain tissue by semiquantitative immunoblot. Here we describe the development and validation of a new method to measure proNGF in the CSF of living patients. This method, based on molecular size separation by capillary electrophoresis, is automated and shows a 40-fold increase in sensitivity with respect to the proNGF immunoblot, largely used in literature, and is robust, specific, and scalable to high-throughput. We have measured proNGF in the cerebrospinal fluid of 84 living patients with AD, 13 controls, and 15 subjective memory complaints (SMC) subjects. By comparing the proNGF levels in the three groups, we found a very significant difference between proNGF levels in AD samples compared with both controls and SMC subjects, while no significant difference was found between SMC and controls. Because of the development of this new immunoassay, we are ready to explore the potentiality of proNGF as a new biomarker for AD or subgroups thereof, as well as for other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
9. The Role of Age on Beta-Amyloid1–42 Plasma Levels in Healthy Subjects.
- Author
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Zecca, Chiara, Pasculli, Giuseppe, Tortelli, Rosanna, Dell'Abate, Maria Teresa, Capozzo, Rosa, Barulli, Maria Rosaria, Barone, Roberta, Accogli, Miriam, Arima, Serena, Pollice, Alessio, Brescia, Vincenzo, and Logroscino, Giancarlo
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AGE groups ,MULTIPLE comparisons (Statistics) ,AGE ,BIOMARKERS - Abstract
Beta-amyloid (Aβ) plaques have been observed in the brain of healthy elderlies with frequencies strongly influenced by age. The aim of the study is to evaluate the role of age and other biochemical and hematological parameters on Aβ
1–42 plasma levels in cognitively and neurologically normal individuals. Two-hundred and seventy-five normal subjects stratified by age groups (<35 years, 35–65 years, and >65 years) were included in the study. Aβ1–42 plasma levels significantly correlated with age (rs = 0.27; p < 0.0001) in the whole sample, inversely correlated with age in the first age group (rs = −0.25, p = 0.01), positively correlated in the second group (rs = 0.22, p = 0.03), while there was no significant correlation in the older group (rs = 0.02, p = 0.86). Both age (β -estimate = 0.08; p < 0.001) and cholesterol (β -estimate = 0.03; p = 0.009) were significantly associated with Aβ1–42 plasma level in multivariable analysis. However, only the association with age survived post hoc adjustment for multiple comparisons. The different effects of age on the Aβ level across age groups should be explored in further studies to better understand the age-dependent variability. This could better define the value of plasma Aβ as a biomarker of the Alzheimer neuropathology. [ABSTRACT FROM AUTHOR]- Published
- 2021
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10. Comparative evaluation of two immunoassays for cerebrospinal fluid β-Amyloid1–42 measurement.
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Zecca, Chiara, Brescia, Vincenzo, Piccininni, Marco, Capozzo, Rosa, Barone, Roberta, Barulli, Maria Rosaria, and Logroscino, Giancarlo
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CEREBROSPINAL fluid examination , *CEREBROSPINAL fluid , *ENZYME-linked immunosorbent assay , *PEARSON correlation (Statistics) , *BLAND-Altman plot , *IMMUNOASSAY , *CHEMILUMINESCENCE immunoassay - Abstract
Beta-Amyloid 1–42 peptide (βA42) is a cerebro-spinal fluid (CSF) biomarker, key element of the NIA Alzheimer's disease diagnostic criteria. The enzyme-linked immunosorbent assay (ELISA) has been the mainstay method for βA42 measurement on cerebrospinal fluid (CSF). Recently, a new βA42 measurement method in chemiluminescence enzyme immunoassay (CLEIA) is available on Lumipulse G 600 II automatic platform. The aim of the work was to evaluate the concordance of the ELISA and the new method (CLEIA) in the CSF βA42 levels measurement. CSF βA42 levels were assayed in 49 samples using the ELISA method (Innotest β- amyloid 1–42, Fujirebio Europe N.V., Gent, Belgium) and CLEIA method on Lumipulse G600II fully automatic platform (Lumipulse G β- amyloid 1–42, Fujirebio Europe N.V., Gent, Belgium). We compared values of the two methods using acceptability interval based on Inherent Combined Imprecision (ICI), the Passing-Bablok regression analysis, the Pearson correlation coefficient (r) and the Bland-Altman plot. The analysis of the ICI showed that the two methods differ substantially. The regression equation (y = −103.04 + 1.52×) highlighted the presence of proportional systematic difference, without significant deviation from linearity (p =.42). The Pearson correlation coefficient was 0.826. The Bland-Altman plot analysis showed a significant systematic difference in the two methods: ELISA measurements were in average –27.06% (95% CI –31.89 to −22.23%) lower compared to CLEIA ones. Our study highlighted a difference between the two methods. Therefore, the cut-off for the normal levels of βA42 should be reviewed in the laboratory report. • The concordance between the CLEIA, a new method for βA42, and ELISA, the mainstay method, was evaluated. • Several statistical approaches and graphical tools (Bland-Altman and Mountain plots) were considered. • A systematic difference between the two methods was found. • The normal limit in the laboratory should be revised based on the new CLEIA method. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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11. Plasma β-amyloid1–42 reference values in cognitively normal subjects.
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Zecca, Chiara, Tortelli, Rosanna, Panza, Francesco, Arcuti, Simona, Piccininni, Marco, Capozzo, Rosa, Barulli, Maria Rosaria, Barone, Roberta, Cardinali, Roberta, Abbrescia, Daniela, Seripa, Davide, Brescia, Vincenzo, and Logroscino, Giancarlo
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REFERENCE values , *AMYLOID , *BLOOD plasma , *BIOMARKERS , *CLINICAL trials , *ALZHEIMER'S disease - Abstract
Background In clinical practice, the use of plasma β-Amyloid1–42 (Aβ 1–42 ) as biomarker for Alzheimer's disease is largely limited by the absence of reference values. The aim of this study was to evaluate Aβ 1–42 plasma concentrations in cognitively normal subjects and to propose reference values. Methods Plasma samples were obtained from 245 subjects, with a wide age-range (19–89 years), enrolled at the Unit of Laboratory Medicine of the “Azienda Ospedaliera Cardinale G. Panico” (younger subjects) and from a population-based study on aging (GreatAGE study) (older subjects). Three different age-groups were established: young (≤ 34), adult (35 ≤ age ≤ 64) and old (>64). The Innogenetics Elisa kit for plasma Aβ 1–42 was used for the analysis. Results The mean (SD) concentration of plasma Aβ 1–42 was 17.65 (5.71) pg/mL. A positive trend was found in Aβ 1–42 levels across the three age groups (p < .0001): young subjects showed values of Aβ 1–42 significantly lower than the adult group (p < .0001) and than the old one (p < .0001 overall); no significant differences were found between the adult and the old groups (p = 1.0000). For the entire cohort the lower limit of 90% Reference Interval, double-sided, was 8.12 pg/mL (95% CI 6.77–9.45) and the upper limit was 29.00 pg/mL (95% CI 27.01–31.00). Conclusion The present study proposes reference values for plasma Aβ 1–42 . Nevertheless, further studies are needed to confirm these results and corroborate the use of these reference values in clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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12. A Novel Splice-Acceptor Site Mutation in GRN (c.709-2 A>T) Causes Frontotemporal Dementia Spectrum in a Large Family from Southern Italy.
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Sassi, Celeste, Capozzo, Rosa, Gibbs, Raphael, Crews, Cynthia, Zecca, Chiara, Arcuti, Simona, Copetti, Massimiliano, Barulli, Maria R., Brescia, Vincenzo, Singleton, Andrew B., and Logroscino, Giancarlo
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FRONTOTEMPORAL dementia ,FRONTOTEMPORAL lobar degeneration ,PROGRANULIN ,GENETIC mutation ,GENETIC testing ,DIAGNOSIS ,GENETICS - Abstract
Heterozygous loss of function mutations in granulin represent a significant cause of frontotemporal lobar degeneration with ubiquitin and TDP-43 inclusions (FTLD-TDP). We report a novel GRN splice site mutation (c.709-2 A>T), segregating with frontotemporal dementia spectrum in a large family from southern Italy. The GRN c.709-2 A>T is predicted to result in the skipping of exon 8, leading to non-sense mediated mRNA decay. Moreover, the PGRN plasma levels in the GRN c.709-2 A>T carriers were significantly lower (24 ng/ml) compared to controls (142.7 ng/ml) or family members non-carriers (82.0 ng/ml) (p-value = 0.005, Kruskal Wallis), suggesting progranulin haploinsufficiency. We do not report any potential pathogenic GRN mutation in a follow-up cohort composed of 6 FTD families and 43 sporadic FTD cases, from the same geographic area. Our study suggests that GRN (c.709-2 A>T) is a novel and likely very rare cause of FTD in this Italian cohort. Finally, in line with previous studies, we show that GRN haploinsufficiency leads to a heterogeneous clinical picture, and plasma progranulin levels may be a reliable tool to identify GRN loss of function mutations. However, given that a) genetic and environmental factors, gender, and age may regulate PGRN plasma levels and b) plasma progranulin levels may not reflect PGRN levels in the central nervous system, we suggest that the measurement of progranulin in the plasma should always be coupled with genetic screening of GRN for mutations. [ABSTRACT FROM AUTHOR]
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- 2016
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13. Tau-Centric Targets and Drugs in Clinical Development for the Treatment of Alzheimer’s Disease.
- Author
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Panza, Francesco, Solfrizzi, Vincenzo, Seripa, Davide, Imbimbo, Bruno P., Lozupone, Madia, Santamato, Andrea, Zecca, Chiara, Barulli, Maria Rosaria, Bellomo, Antonello, Pilotto, Alberto, Daniele, Antonio, Greco, Antonio, and Logroscino, Giancarlo
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ALZHEIMER'S disease ,BIOAVAILABILITY ,CEREBRAL circulation ,COGNITION ,DEMENTIA ,METHYLENE blue ,NERVE tissue proteins ,PHOSPHATASES ,PHOSPHOTRANSFERASES ,TOXICITY testing ,DRUG development ,CHEMICAL inhibitors ,THERAPEUTICS - Abstract
The failure of several Phase II/III clinical trials in Alzheimer’s disease (AD) with drugs targeting β-amyloid accumulation in the brain fuelled an increasing interest in alternative treatments against tau pathology, including approaches targeting tau phosphatases/kinases, active and passive immunization, and anti-tau aggregation. The most advanced tau aggregation inhibitor (TAI) is methylthioninium (MT), a drug existing in equilibrium between a reduced (leuco-methylthioninium) and oxidized form (MT
+ ). MT chloride (methylene blue) was investigated in a 24-week Phase II clinical trial in 321 patients with mild to moderate AD that failed to show significant positive effects in mild AD patients, although long-term observations (50 weeks) and biomarker studies suggested possible benefit. The dose of 138 mg/day showed potential benefits on cognitive performance of moderately affected AD patients and cerebral blood flow in mildly affected patients. Further clinical evidence will come from the large ongoing Phase III trials for the treatment of AD and the behavioral variant of frontotemporal dementia on a new form of this TAI, more bioavailable and less toxic at higher doses, called TRx0237. More recently, inhibitors of tau acetylation are being actively pursued based on impressive results in animal studies obtained by salsalate, a clinically used derivative of salicylic acid. [ABSTRACT FROM AUTHOR]- Published
- 2016
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14. A New Presenilin 1 (Psen1) Mutation (p.Cys263Trp) as a Cause of Both Early and Late-Onset Alzheimer's Disease in a Large Italian Family.
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Tortelli, Rosanna, Seripa, Davide, Zecca, Chiara, Dell'Abate, Maria Teresa, Bisceglia, Paola, Barulli, Maria Rosaria, De Blasi, Roberto, and Logroscino, Giancarlo
- Subjects
ALZHEIMER'S disease ,LEWY body dementia ,SYMPTOMS ,PHENOTYPIC plasticity ,MISSENSE mutation - Abstract
Mutations in the PSEN1 gene are the most common cause of autosomal dominant Alzheimer's disease, and are characterized by a high phenotype variability. This study describes a five-generation family, with a prevalent late-onset of the disease and a high frequency of depression, in which a new missense mutation (c.789T > G, p.Cys263Trp) in exon 8 of the PSEN1 gene was found. Only the proband presented an early onset at the age of 45 with attention deficit, followed by spatial disorientation, psychiatric symptoms and parkinsonian signs. The other two cases had a late onset of the disease and a typical presentation with memory loss. Both were characterized by a high level of anxiety and depression. The disease course was different with signs of Lewy body dementia for the proband's mother, and pyramidal involvement and a shorter disease duration for the proband's maternal aunt. The other eight cases with late-onset dementia and three cases with a long history of depression have been reported in the family pedigree, underlying the high phenotype variability of PSEN1 mutations. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
15. Response to Letter to the Editor: "Plasma β-amyloid1–42 reference values".
- Author
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Zecca, Chiara, Brescia, Vincenzo, Panza, Francesco, and Logroscino, Giancarlo
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REFERENCE values - Published
- 2019
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16. proNGF Measurement in Cerebrospinal Fluid Samples of a Large Cohort of Living Patients With Alzheimer's Disease by a New Automated Immunoassay
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Francesca Malerba, Ivan Arisi, Rita Florio, Chiara Zecca, Maria Teresa Dell'Abate, Bruno Bruni Ercole, Serena Camerini, Marialuisa Casella, Giancarlo Logroscino, Antonino Cattaneo, Malerba, Francesca, Arisi, Ivan, Florio, Rita, Zecca, Chiara, Dell'Abate, Maria Teresa, Bruni Ercole, Bruno, Camerini, Serena, Casella, Marialuisa, Logroscino, Giancarlo, and Cattaneo, Antonino
- Subjects
Oncology ,Aging ,medicine.medical_specialty ,diagnosis ,Cognitive Neuroscience ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Disease ,Settore BIO/09 - Fisiologia ,Cerebrospinal fluid ,neurodegenerative disease ,Internal medicine ,medicine ,Diagnostic biomarker ,neurodegenerative diseases ,proNGF ,immunoassay ,Original Research ,medicine.diagnostic_test ,business.industry ,Significant difference ,Alzheimer's disease ,Large cohort ,diagnosi ,Immunoassay ,Biomarker (medicine) ,biomarker ,Automated immunoassay ,business ,RC321-571 ,Neuroscience - Abstract
The discovery of new biomarkers for Alzheimer's disease (AD) is essential for an accurate diagnosis, to conceive new strategies of treatments, and for monitoring the efficacy of potential disease-modifying therapies in clinical trials. proNGF levels in the cerebrospinal fluid (CSF) represent a promising diagnostic biomarker for AD, but its validation was hampered by the absence of a reliable immunoassay. In the literature, proNGF is currently measured in postmortem brain tissue by semiquantitative immunoblot. Here we describe the development and validation of a new method to measure proNGF in the CSF of living patients. This method, based on molecular size separation by capillary electrophoresis, is automated and shows a 40-fold increase in sensitivity with respect to the proNGF immunoblot, largely used in literature, and is robust, specific, and scalable to high-throughput. We have measured proNGF in the cerebrospinal fluid of 84 living patients with AD, 13 controls, and 15 subjective memory complaints (SMC) subjects. By comparing the proNGF levels in the three groups, we found a very significant difference between proNGF levels in AD samples compared with both controls and SMC subjects, while no significant difference was found between SMC and controls. Because of the development of this new immunoassay, we are ready to explore the potentiality of proNGF as a new biomarker for AD or subgroups thereof, as well as for other neurodegenerative diseases.
- Published
- 2021
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