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Article ; Online: Neurofilaments as Decay Rate Biomarker in Spinocerebellar Ataxia Type 1: Highlighting Key Questions of Application and Future Challenges.

Nacmias, Benedetta

2022 Volume 98, Issue 20, Page(s) 821–822

MeSH term(s)	Biomarkers ; Disease Progression ; Humans ; Intermediate Filaments ; Spinocerebellar Ataxias/diagnosis ; Spinocerebellar Ataxias/genetics
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-03-09
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000200360
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Article ; Online: Does diet matter? The implications of dietary habits for dementia.

Peters, Nils / Nacmias, Benedetta

Neurology

2022

Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Editorial
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000201420
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Article ; Online: The Association Between Positive Amyloid-PET and Cognitive Decline Is Not Always Supportive of Alzheimer's Disease: Suggestions from a Case Report.

Lombardi, Gemma / Berti, Valentina / Ginestroni, Andrea / Nacmias, Benedetta / Sorbi, Sandro

Journal of Alzheimer's disease reports

2024 Volume 8, Issue 1, Page(s) 281–288

Abstract: Amyloid-β deposition is the pathological hallmark of both cerebral amyloid angiopathy and Alzheimer's disease dementia, clinical conditions that can share cognitive decline and positive Amyloid-PET scan. A case is reported involving an 82-year-old ... ...

Abstract	Amyloid-β deposition is the pathological hallmark of both cerebral amyloid angiopathy and Alzheimer's disease dementia, clinical conditions that can share cognitive decline and positive Amyloid-PET scan. A case is reported involving an 82-year-old Italian female who presented initially a memory deficit, later transient focal neurologic episodes, and finally two symptomatic lobar intracerebral hemorrhages. In light of these events, MRI and PET imaging findings, acquired before cerebral hemorrhages, are reconsidered and discussed, highlighting the utility of Amyloid-PET in supporting an
Language	English
Publishing date	2024-02-16
Publishing country	Netherlands
Document type	Case Reports
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-230183
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Article ; Online: Creutzfeldt-Jakob Disease in a Patient with Previous COVID-19 Infection: "The Virus Caused the Derangement in My Brain".

Leccese, Deborah / Cornacchini, Sara / Nacmias, Benedetta / Sorbi, Sandro / Bessi, Valentina

Journal of Alzheimer's disease reports

2023 Volume 7, Issue 1, Page(s) 129–134

Abstract: Recent studies have speculated a link between Creutzfeldt-Jakob disease (CJD) and COVID-19, following the description of CJD cases after COVID-19 infection. We report the case of a 71-year-old female patient who developed neuropsychiatric and ... ...

Abstract	Recent studies have speculated a link between Creutzfeldt-Jakob disease (CJD) and COVID-19, following the description of CJD cases after COVID-19 infection. We report the case of a 71-year-old female patient who developed neuropsychiatric and neurological symptoms after COVID-19 infection and was later diagnosed with CJD. Cerebrospinal fluid (CSF) total tau levels were slightly increased. She resulted prion protein gene (PRNP) M129V heterozygous. We aim to emphasize the role of the polymorphism at codon 129 of PRNP gene on the clinical phenotype and duration of CJD, and the CSF total tau levels that likely correlate with the rate of disease progression.
Language	English
Publishing date	2023-02-14
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-220095
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Article ; Online: The Huntington's Disease Gene in an Italian Cohort of Patients with Bipolar Disorder.

Ferrari, Camilla / Capacci, Elena / Bagnoli, Silvia / Ingannato, Assunta / Sorbi, Sandro / Nacmias, Benedetta

Genes

2023 Volume 14, Issue 9

Abstract: Background and objectives: Huntington's disease (HD) is characterized by motor, cognitive and psychiatric manifestations and caused by an expansion of CAG repeats over 35 triplets on the huntingtin (: Methods: We assessed the : Results: No patient ...

Abstract	Background and objectives: Huntington's disease (HD) is characterized by motor, cognitive and psychiatric manifestations and caused by an expansion of CAG repeats over 35 triplets on the huntingtin ( Methods: We assessed the Results: No patient was found to be a carrier of the pathological Conclusion: The pathological
MeSH term(s)	Humans ; Bipolar Disorder/genetics ; Huntington Disease/genetics ; Alleles ; Genotype ; Family
Language	English
Publishing date	2023-08-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14091681
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Article: Plasma GFAP, NfL and pTau 181 detect preclinical stages of dementia.

Ingannato, Assunta / Bagnoli, Silvia / Mazzeo, Salvatore / Giacomucci, Giulia / Bessi, Valentina / Ferrari, Camilla / Sorbi, Sandro / Nacmias, Benedetta

Frontiers in endocrinology

2024 Volume 15, Page(s) 1375302

Abstract: Background: Plasma biomarkers are preferable to invasive and expensive diagnostic tools, such as neuroimaging and lumbar puncture that are gold standard in the clinical management of Alzheimer's Disease (AD). Here, we investigated plasma Glial ... ...

Abstract	Background: Plasma biomarkers are preferable to invasive and expensive diagnostic tools, such as neuroimaging and lumbar puncture that are gold standard in the clinical management of Alzheimer's Disease (AD). Here, we investigated plasma Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Chain (NfL) and Phosphorylated-tau-181 (pTau 181) in AD and in its early stages: Subjective cognitive decline (SCD) and Mild cognitive impairment (MCI). Material and methods: This study included 152 patients (42 SCD, 74 MCI and 36 AD). All patients underwent comprehensive clinical and neurological assessment. Blood samples were collected for Apolipoprotein E (APOE) genotyping and plasma biomarker (GFAP, NfL, and pTau 181) measurements. Forty-three patients (7 SCD, 27 MCI, and 9 AD) underwent a follow-up (FU) visit after 2 years, and a second plasma sample was collected. Plasma biomarker levels were detected using the Simoa SR-X technology (Quanterix Corp.). Statistical analysis was performed using SPSS software version 28 (IBM SPSS Statistics). Statistical significance was set at p < 0.05. Results: GFAP, NfL and pTau 181 levels in plasma were lower in SCD and MCI than in AD patients. In particular, plasma GFAP levels were statistically significant different between SCD and AD ( Discussion and conclusions: Plasma GFAP, NfL and pTau 181 are promising biomarkers in the diagnosis of the prodromic stages and prognosis of dementia.
MeSH term(s)	Humans ; Glial Fibrillary Acidic Protein/blood ; Female ; Male ; Neurofilament Proteins/blood ; tau Proteins/blood ; Aged ; Biomarkers/blood ; Cognitive Dysfunction/blood ; Cognitive Dysfunction/diagnosis ; Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Middle Aged ; Phosphorylation ; Dementia/blood ; Dementia/diagnosis ; Apolipoproteins E/blood ; Apolipoproteins E/genetics ; Aged, 80 and over ; Follow-Up Studies
Chemical Substances	Glial Fibrillary Acidic Protein ; Neurofilament Proteins ; tau Proteins ; Biomarkers ; neurofilament protein L ; GFAP protein, human ; Apolipoproteins E ; MAPT protein, human
Language	English
Publishing date	2024-04-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2024.1375302
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Article ; Online: Intermediate alleles of HTT: A new pathway in longevity.

Ingannato, Assunta / Bagnoli, Silvia / Bessi, Valentina / Ferrari, Camilla / Mazzeo, Salvatore / Sorbi, Sandro / Nacmias, Benedetta

Journal of the neurological sciences

2022 Volume 438, Page(s) 120274

Abstract: Centenarians are the best example of successful aging, reaching extreme longevity escaping age-related diseases. Genome sequencing studies provided evidence for genetic factors linked to heathy long life, including genes related to age-dependent diseases. ...

Abstract	Centenarians are the best example of successful aging, reaching extreme longevity escaping age-related diseases. Genome sequencing studies provided evidence for genetic factors linked to heathy long life, including genes related to age-dependent diseases. HTT (Huntingtin) gene is linked to Huntington's Disease, but also associated to longevity in capuchins and mice. HTT Intermediate alleles (IAs) are defined as CAG repeat expansion between 27 and 35. According to recent data IAs might increase Alzheimer's Disease risk, but also might have a neuroprotective effect and can confer an advantage in brain development. Here, we investigated, for the first time, the possible implication of HTT IAs in extreme longevity and their possible association in cognitive decline. We analysed the distribution of IAs in Italian Centenarians (n = 143) and compared with pathological controls with cognitive decline (n = 232, including 80 Alzheimer's Disease, 78 Frontotemporal Dementia and 74 Subjective Cognitive Decline patients) and healthy controls (n = 104). Our data show a statistically significant higher frequency of IAs in Centenarians with respect to pathological controls with cognitive decline (p = .031; OR = 2.3097 95% CI 1.0591 to 5.0371), with a percentage of 11.2 respect to 5.4 respectively. The highest presence of IAs in Centenarians confirms and extends in humans a possible implication of HTT gene in exceptional lifespan and in brain development with a neuroprotective effect.
MeSH term(s)	Aged, 80 and over ; Alleles ; Alzheimer Disease/genetics ; Animals ; Humans ; Huntingtin Protein/genetics ; Huntington Disease/genetics ; Longevity/genetics ; Mice
Chemical Substances	HTT protein, human ; Huntingtin Protein
Language	English
Publishing date	2022-05-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80160-4
ISSN	1878-5883 ; 0022-510X ; 0374-8642
ISSN (online)	1878-5883
ISSN	0022-510X ; 0374-8642
DOI	10.1016/j.jns.2022.120274
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Article ; Online: GRN Missense Variants and Familial Alzheimer's Disease: Two Case Reports.

Ingannato, Assunta / Bessi, Valentina / Chiari, Annalisa / Salvatori, Davide / Bagnoli, Silvia / Bedin, Roberta / Ferrari, Camilla / Sorbi, Sandro / Nacmias, Benedetta

Journal of Alzheimer's disease : JAD

2023 Volume 96, Issue 2, Page(s) 767–775

Abstract: Background: Progranulin protein (GRN) is a growth factor, encoded by the GRN (Granulin precursor) gene, involved in several functions including inflammation, wound repair, signal transduction, proliferation, and tumorigenesis. Mutations in GRN gene are ... ...

Abstract	Background: Progranulin protein (GRN) is a growth factor, encoded by the GRN (Granulin precursor) gene, involved in several functions including inflammation, wound repair, signal transduction, proliferation, and tumorigenesis. Mutations in GRN gene are usually the genetic etiology of frontotemporal dementia (FTD), but different studies reported GRN mutations in Alzheimer 's disease (AD) patients. Objective: Here, we analyzed FTD linked gene GRN in 23 patients with a clinical diagnosis of AD and a family history of AD (FAD), not carrying mutations in AD candidate genes (PSEN 1, PSEN 2, and APP). In addition, Microtubule-associated protein tau (MAPT) gene was studied too. All patients underwent an extensive neuropsychological battery. Methods: Genetic analyses were performed thought PCR assay and sequencing. Variants were annotated with ANNOVAR and allele frequency was checked on population databases. In silico prediction tools were consulted to check nonsynonymous variants and their effect on protein function and structure. The clinical data were retrospectively collected from medical records. Results: Genetic screening of MAPT and GRN in 23 FAD patients highlighted two rare different variants in two probands (2/23 = 8,7%) located in GRN gene: R433W (p.Arg433Trp) and C521Y (p.Cys521Tyr). The R433W and C521Y are variants with uncertain significant, that are predicted to affect GRN protein structure and function, with a possible damaging effect. Conclusions: Our data provide evidence of the importance of GRN genetic analysis also in the study of familial AD.
MeSH term(s)	Humans ; Alzheimer Disease/genetics ; Frontotemporal Dementia/genetics ; Retrospective Studies ; Intercellular Signaling Peptides and Proteins/genetics ; Progranulins/genetics ; Mutation/genetics
Chemical Substances	Intercellular Signaling Peptides and Proteins ; Progranulins ; GRN protein, human
Language	English
Publishing date	2023-10-29
Publishing country	Netherlands
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-230689
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Article ; Online: Multilayered Bioorthogonal SERS Nanoprobes Selectively Aggregating in Human Fluids: A Smart Optical Assay for β-Amyloid Peptide Quantification.

Dallari, Caterina / Lenci, Elena / Trabocchi, Andrea / Bessi, Valentina / Bagnoli, Silvia / Nacmias, Benedetta / Credi, Caterina / Pavone, Francesco Saverio

ACS sensors

2023 Volume 8, Issue 10, Page(s) 3693–3700

Abstract: Alzheimer's disease (AD) is a debilitating neurological condition characterized by cognitive decline, memory loss, and behavioral skill impairment, features that worsen with time. Early diagnosis will likely be the most effective therapy for Alzheimer's ... ...

Abstract	Alzheimer's disease (AD) is a debilitating neurological condition characterized by cognitive decline, memory loss, and behavioral skill impairment, features that worsen with time. Early diagnosis will likely be the most effective therapy for Alzheimer's disease since it can ensure timely pharmacological treatments that can reduce the irreversible progression and delay the symptoms. Amyloid β-peptide 1-42 (Aβ (1-42)) is considered one of the key pathological AD biomarkers that is present in different biological fluids. However, Aβ (1-42) detection still relies on colorimetric and enzyme-linked immunoassays as the gold standard characterized by low accuracy or high costs, respectively. In this context, optical detection techniques based on surface-enhanced Raman spectroscopy (SERS) through advanced nanoconstructs are promising alternatives for the development of novel rapid and low-cost methods for the targeting of Aβ pathological biomarkers in fluids. Here, a multilayered nanoprobe constituted by bioorthogonal Raman reporters (RRs) embedded within two layers of gold nanoparticles (Au@RRs@AuNPs) has been developed and successfully validated for specific detection of Aβ (1-42) in the human cerebrospinal fluid (CSF) with sensitivity down to pg/mL. The smart double-layer configuration enables us to exploit the outer gold NP surfaces for selective absorption of targeted peptide whose concentration controls the aggregation behavior of Au@RRs@AuNPs, proportionally reflected in Raman intensity changes, providing high specificity and sensitivity and representing a significant step ahead of the state of the art on SERS for clinical analyses.
MeSH term(s)	Humans ; Amyloid beta-Peptides/cerebrospinal fluid ; Alzheimer Disease/diagnosis ; Alzheimer Disease/cerebrospinal fluid ; Gold ; Metal Nanoparticles/chemistry ; Biomarkers
Chemical Substances	Amyloid beta-Peptides ; Gold (7440-57-5) ; Biomarkers
Language	English
Publishing date	2023-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.3c00225
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Article ; Online: Understanding the interplay between APO E polymorphism and cognition in the Italian oldest old: results from the "Mugello study".

Lombardi, Gemma / Pancani, Silvia / Bagnoli, Silvia / Vannetti, Federica / Nacmias, Benedetta / Sorbi, Sandro / Cecchi, Francesca / Macchi, Claudio

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2023 Volume 45, Issue 2, Page(s) 539–546

Abstract: Introduction: Recent data suggest that the deleterious effect on general health and cognition of ε4 allele of Apolipoprotein E (ApoE) observed in the elderly population, may attenuate in extreme aging. This study aimed to describe the ApoE genotype ... ...

Abstract	Introduction: Recent data suggest that the deleterious effect on general health and cognition of ε4 allele of Apolipoprotein E (ApoE) observed in the elderly population, may attenuate in extreme aging. This study aimed to describe the ApoE genotype distribution and its relationship with cognition in a group of nonagenarians living in the Mugello area, Italy. Material and methods: Cognition was evaluated using the Mini-Mental-State-Examination (MMSE). DNA was extracted from blood samples to determine ApoE genotyping. Participants were classified into three ApoE groups (ε2, ε3, ε4). Logistic and linear regression models were created, to assess the relationship between ApoE genotype group and dementia diagnosis and cognitive performance, respectively. Results: 169 subjects were included. ApoE ε3 was the most prevalent genotype (76.3%). Dementia prevalence was 26.6% and it was not associated with the presence of ApoE ε4. Participants of ε4 group were significantly more likely to have lower cognitive performances than ε2 and ε3, independently of a dementia diagnosis. Discussion: Results support that ApoE genotype no longer plays a role in the health condition of the oldest old, however, an interaction is detectable between ApoE polymorphism and cognitive performances at this extreme age.
MeSH term(s)	Aged ; Aged, 80 and over ; Humans ; Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Cognition ; Dementia ; Genotype ; Polymorphism, Genetic/genetics
Chemical Substances	Apolipoprotein E4 ; Apolipoproteins E ; ApoE protein, human
Language	English
Publishing date	2023-09-15
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-023-07073-4
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