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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: The complexity of Alzheimer's disease: an evolving puzzle.

Ferrari, Camilla / Sorbi, Sandro

Physiological reviews

2021 Volume 101, Issue 3, Page(s) 1047–1081

Abstract: The history of Alzheimer's disease (AD) started in 1907, but we needed to wait until the end of the century to identify the components of pathological hallmarks and genetic subtypes and to formulate the first pathogenic hypothesis. Thanks to biomarkers ... ...

Abstract	The history of Alzheimer's disease (AD) started in 1907, but we needed to wait until the end of the century to identify the components of pathological hallmarks and genetic subtypes and to formulate the first pathogenic hypothesis. Thanks to biomarkers and new technologies, the concept of AD then rapidly changed from a static view of an amnestic dementia of the presenium to a biological entity that could be clinically manifested as normal cognition or dementia of different types. What is clearly emerging from studies is that AD is heterogeneous in each aspect, such as amyloid composition, tau distribution, relation between amyloid and tau, clinical symptoms, and genetic background, and thus it is probably impossible to explain AD with a single pathological process. The scientific approach to AD suffers from chronological mismatches between clinical, pathological, and technological data, causing difficulty in conceiving diagnostic gold standards and in creating models for drug discovery and screening. A recent mathematical computer-based approach offers the opportunity to study AD in real life and to provide a new point of view and the final missing pieces of the AD puzzle.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Biomarkers/metabolism ; Brain/metabolism ; Brain/pathology ; Humans ; Peptide Fragments/metabolism ; Plaque, Amyloid/diagnosis ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/pathology
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments
Language	English
Publishing date	2021-01-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00015.2020
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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: Understanding the role of self-attention in a Transformer model for the discrimination of SCD from MCI using resting-state EEG.

Sibilano, Elena / Buongiorno, Domenico / Lassi, Michael / Grippo, Antonello / Bessi, Valentina / Sorbi, Sandro / Mazzoni, Alberto / Bevilacqua, Vitoantonio / Brunetti, Antonio

IEEE journal of biomedical and health informatics

2024 Volume PP

Abstract: The identification of EEG biomarkers to discriminate Subjective Cognitive Decline (SCD) from Mild Cognitive Impairment (MCI) conditions is a complex task which requires great clinical effort and expertise. We exploit the self-attention component of the ... ...

Abstract	The identification of EEG biomarkers to discriminate Subjective Cognitive Decline (SCD) from Mild Cognitive Impairment (MCI) conditions is a complex task which requires great clinical effort and expertise. We exploit the self-attention component of the Transformer architecture to obtain physiological explanations of the model's decisions in the discrimination of 56 SCD and 45 MCI patients using resting-state EEG. Specifically, an interpretability workflow leveraging attention scores and time-frequency analysis of EEG epochs through Continuous Wavelet Transform is proposed. In the classification framework, models are trained and validated with 5-fold cross-validation and evaluated on a test set obtained by selecting 20% of the total subjects. Ablation studies and hyperparameter tuning tests are conducted to identify the optimal model configuration. Results show that the best performing model, which achieves acceptable results both on epochs' and patients' classification, is capable of finding specific EEG patterns that highlight changes in the brain activity between the two conditions. We demonstrate the potential of attention weights as tools to guide experts in understanding which disease-relevant EEG features could be discriminative of SCD and MCI.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2695320-1
ISSN	2168-2208 ; 2168-2194
ISSN (online)	2168-2208
ISSN	2168-2194
DOI	10.1109/JBHI.2024.3390606
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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: 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: Beta-amyloid immunisation in Alzheimer's disease.

Sorbi, S

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

2005 Volume 26 Suppl 1, Page(s) S5

MeSH term(s)	Alzheimer Disease/immunology ; Alzheimer Disease/therapy ; Amyloid beta-Peptides/immunology ; Humans ; Immunotherapy/methods ; Lymphocyte Activation ; Peptide Fragments/immunology
Chemical Substances	Amyloid beta-Peptides ; Peptide Fragments ; amyloid beta-protein (1-42)
Language	English
Publishing date	2005-05
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/s10072-005-0388-7
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Zs.A 1877: Show issues

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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: Exploring depression in Parkinson's disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management.

Stocchi, Fabrizio / Angelo Antonini / Barone, Paolo / Bellelli, Giuseppe / Fagiolini, Andrea / Ferini Strambi, Luigi / Sorbi, Sandro / Padovani, Alessandro

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

2023 Volume 44, Issue 9, Page(s) 3123–3131

Abstract: Background: Depression is a prodromic and a frequent non-motor symptom of Parkinson's disease, associated to reduced quality of life and poor outcomes. The diagnosis of depression in parkinsonian patients represents a challenge due to the overlapping of ...

Abstract	Background: Depression is a prodromic and a frequent non-motor symptom of Parkinson's disease, associated to reduced quality of life and poor outcomes. The diagnosis of depression in parkinsonian patients represents a challenge due to the overlapping of symptoms typical of the two conditions. Methods: A Delphi panel survey was performed to reach a consensus amongst different Italian specialists on four main topics: the neuropathological correlates of depression, main clinical aspects, diagnosis, and management of depression in Parkinson's disease. Results and conclusion: Experts have recognized that depression is an established risk factor of PD and that its anatomic substrate is related to the neuropathological abnormalities typical of the disease. Multimodal and SSRI antidepressant have been confirmed as a valid therapeutic option in the treatment of depression in PD. Tolerability, safety profile, and potential efficacy on broad spectrum of symptoms of depression including cognitive symptoms and anhedonia should be considered when selecting an antidepressant and the choice should be tailored on the patients' characteristics.
MeSH term(s)	Humans ; Parkinson Disease/complications ; Parkinson Disease/diagnosis ; Parkinson Disease/therapy ; Depression/diagnosis ; Depression/etiology ; Depression/therapy ; Consensus ; Quality of Life ; Delphi Technique ; Antidepressive Agents/therapeutic use
Chemical Substances	Antidepressive Agents
Language	English
Publishing date	2023-04-27
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/s10072-023-06740-w
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