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Article: Exploring Neurofilament Light Chain and Exosomes in the Genetic Forms of Frontotemporal Dementia.

Zanardini, Roberta / Saraceno, Claudia / Benussi, Luisa / Squitti, Rosanna / Ghidoni, Roberta

2022 Volume 16, Page(s) 758182

Abstract: Differential diagnosis of neurological disorders and their subtype classification are challenging without specific biomarkers. Genetic forms of these disorders, typified by an autosomal dominant family history, could offer a window to identify potential ... ...

Abstract	Differential diagnosis of neurological disorders and their subtype classification are challenging without specific biomarkers. Genetic forms of these disorders, typified by an autosomal dominant family history, could offer a window to identify potential biomarkers by exploring the presymptomatic stages of the disease. Frontotemporal dementia (FTD) is the second cause of dementia with an age of onset < 65, and its most common mutations are in
Language	English
Publishing date	2022-01-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.758182
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Article ; Online: CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia.

Tournier, Benjamin B / Sorce, Silvia / Marteyn, Antoine / Ghidoni, Roberta / Benussi, Luisa / Binetti, Giuliano / Herrmann, François R / Krause, Karl-Heinz / Zekry, Dina

Alzheimer's & dementia : the journal of the Alzheimer's Association

2023 Volume 20, Issue 1, Page(s) 124–135

Abstract: Introduction: As the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia.: Methods: Logistic regression models with CCR5/ ...

Abstract	Introduction: As the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia. Methods: Logistic regression models with CCR5/apolipoprotein E (ApoE) polymorphisms were applied on a sample of 205 cognitively normal individuals and 189 dementia patients from Geneva. The impact of oxidative stress on Ccr5 expression and cell death was assessed in mice neurons. Results: CCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an 11-fold greater risk of vascular-and-mixed dementia. Oxidative stress-induced cell death in Ccr5 Discussion: We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.
MeSH term(s)	Humans ; Animals ; Mice ; Dementia, Vascular/genetics ; Resilience, Psychological ; Genotype ; Chemokines ; Polymorphism, Genetic ; Receptors, CCR5/genetics
Chemical Substances	Chemokines ; CCR5 protein, human ; Receptors, CCR5
Language	English
Publishing date	2023-07-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13392
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Article: Genome Wide Association Study and Next Generation Sequencing: A Glimmer of Light Toward New Possible Horizons in Frontotemporal Dementia Research.

Ciani, Miriam / Benussi, Luisa / Bonvicini, Cristian / Ghidoni, Roberta

Frontiers in neuroscience

2019 Volume 13, Page(s) 506

Abstract: Frontotemporal Dementia (FTD) is a focal neurodegenerative disease, with a strong genetic background, that causes early onset dementia. The present knowledge about the risk loci and causative mutations of FTD mainly derives from genetic linkage analysis, ...

Abstract	Frontotemporal Dementia (FTD) is a focal neurodegenerative disease, with a strong genetic background, that causes early onset dementia. The present knowledge about the risk loci and causative mutations of FTD mainly derives from genetic linkage analysis, studies of candidate genes, Genome-Wide Association Studies (GWAS) and Next-Generation Sequencing (NGS) applications. In this review, we report recent insights into the genetics of FTD, and, specifically, the results achieved thanks to GWAS and NGS approaches. Linkage studies of large FTD pedigrees have prompted the identification of causal mutations in different genes: mutations in
Language	English
Publishing date	2019-05-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2019.00506
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Article ; Online: Neurodevelopmental disorders: Metallomics studies for the identification of potential biomarkers associated to diagnosis and treatment.

Scassellati, Catia / Bonvicini, Cristian / Benussi, Luisa / Ghidoni, Roberta / Squitti, Rosanna

Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)

2020 Volume 60, Page(s) 126499

Abstract: Background: Diagnosis and treatment of complex diseases such as Neurodevelopmental Disorders (NDDs) can be resolved through the identification of biomarkers. Metallomics (research on biometals) and metallomes (metalloproteins/metalloenzymes/chaperones) ... ...

Abstract	Background: Diagnosis and treatment of complex diseases such as Neurodevelopmental Disorders (NDDs) can be resolved through the identification of biomarkers. Metallomics (research on biometals) and metallomes (metalloproteins/metalloenzymes/chaperones) along with genomics, proteomics and metabolomics, can contribute to accelerate and improve this process. Aim: This review focused on four NDDs pathologies (Schizophrenia, SZ; Attention Deficit Hyperactivity Disorder, ADHD; Autism, ADS; Epilepsy), and we reported, for the first time, different studies on the role played by the principal six essential trace elements (Cobalt, Co; Copper, Cu; Iron, Fe; Manganese, Mn; Selenium, Se; Zinc, Zn) that can influence diagnosis/treatment. Results: in light of the literature presented, based on meta-analyses, we suggest that Zn (glutamatergic neurotransmission, inflammation, neurodegeneration, autoimmunity alterations), could be a potential diagnostic biomarker associated to SZ. Moreover, considering the single association studies going in the same direction, increased Cu (catecholamine alterations, glucose intolerance, altered lipid metabolism/oxidative stress) and lower Fe (dopaminergic dysfunctions) levels were associated with a specific negative symptomatology. Lower Mn (lipid metabolism/oxidative stress alterations), and lower Se (metabolic syndrome) were linked to SZ. From the meta-analyses in ADHD, it is evidenced that Fe (and ferritin in particular), Mn, and Zn (oxidative stress dysfunctions) could be potential diagnostic biomarkers, mainly associated to severe hyperactive or inattentive symptoms; as well as Cu, Fe, Zn in ADS and Zn in Epilepsy. Fe, Zn and Mn levels seem to be influenced by antipsychotics treatment in SZ; Mn and Zn by methylphenidate treatment in ADHD; Cu and Zn by antiepileptic drugs in Epilepsy. Conclusions: Although there is controversy and further studies are needed, this work summarizes the state of art of the literature on this topic. We claim to avoid underreporting the impact of essential trace elements in paving the way for biomarkers research for NDDs.
MeSH term(s)	Biomarkers/analysis ; Humans ; Neurodevelopmental Disorders/diagnosis ; Neurodevelopmental Disorders/drug therapy ; Trace Elements/analysis
Chemical Substances	Biomarkers ; Trace Elements
Language	English
Publishing date	2020-03-16
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1236267-0
ISSN	1878-3252 ; 1611-602X ; 0946-672X
ISSN (online)	1878-3252 ; 1611-602X
ISSN	0946-672X
DOI	10.1016/j.jtemb.2020.126499
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Ghidoni, Roberta / Squitti, Rosanna / Siotto, Mariacristina / Benussi, Luisa

Journal of Alzheimer's disease : JAD

2018 Volume 62, Issue 4, Page(s) 1507–1518

Abstract: The criteria for the clinical diagnosis of AD include the analysis of biomarkers of the underlying brain disease pathology; a set of cerebrospinal fluid (CSF) tests, amyloid-β1-42 (Aβ42), total-tau (t-tau), and phosphorylated tau (p-tau), are available ... ...

Abstract	The criteria for the clinical diagnosis of AD include the analysis of biomarkers of the underlying brain disease pathology; a set of cerebrospinal fluid (CSF) tests, amyloid-β1-42 (Aβ42), total-tau (t-tau), and phosphorylated tau (p-tau), are available and their performance in a clinical setting has been assessed in several studies. Thus, in dementia research, great advances have been made in the discovery of putative biomarkers; however, disappointingly, few of them have been translated into clinically applicable assays. To find biomarkers able to reliably detect AD pathology already at prodromal stages and in blood is even more important. Recent technical breakthroughs have provided ultrasensitive methods that allow the detection of brain-specific proteins in blood. In the present review, we will focus on the usefulness of ultrasensitive technologies for biomarker discovery and trace elements detection; moreover, we will review studies on circulating nano-compartments, a promising novel source of material for molecular diagnostics.
MeSH term(s)	Alzheimer Disease/metabolism ; Biomarkers/metabolism ; Humans
Chemical Substances	Biomarkers
Language	English
Publishing date	2018-03-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-170953
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Article: Disclosure of Genetic Risk Factors for Alzheimer's Disease to Cognitively Healthy Individuals-From Current Practice towards a Personalised Medicine Scenario.

Galluzzi, Samantha / Pievani, Michela / Zanetti, Orazio / Benussi, Luisa / The Italian-DIAfN Working Group / Frisoni, Giovanni B / Di Maria, Emilio

Biomedicines

2022 Volume 10, Issue 12

Abstract: Alzheimer's disease (AD) is a genetically complex disorder. In addition to the relatively small number of pathogenic variants causing autosomal dominant AD, many others have been associated with the much more common sporadic form. The E4 allele of the ... ...

Abstract	Alzheimer's disease (AD) is a genetically complex disorder. In addition to the relatively small number of pathogenic variants causing autosomal dominant AD, many others have been associated with the much more common sporadic form. The E4 allele of the Apolipoprotein E (
Language	English
Publishing date	2022-12-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10123177
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Article ; Online: Regulatory miRNAs in Cardiovascular and Alzheimer's Disease: A Focus on Copper.

Sacco, Anna / Martelli, Fabio / Pal, Amit / Saraceno, Claudia / Benussi, Luisa / Ghidoni, Roberta / Rongioletti, Mauro / Squitti, Rosanna

International journal of molecular sciences

2022 Volume 23, Issue 6

Abstract: Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), are key regulators of differentiation and development. In the cell, transcription factors regulate the production of miRNA in response to different external stimuli. Copper (Cu) is a heavy metal and ...

Abstract	Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), are key regulators of differentiation and development. In the cell, transcription factors regulate the production of miRNA in response to different external stimuli. Copper (Cu) is a heavy metal and an essential micronutrient with widespread industrial applications. It is involved in a number of vital biological processes encompassing respiration, blood cell line maturation, and immune responses. In recent years, the link between deregulation of miRNAs' functionality and the development of various pathologies as well as cardiovascular diseases (CVDs) has been extensively studied. Alzheimer's disease (AD) is the most common cause of dementia in the elderly with a complex disease etiology, and its link with Cu abnormalities is being increasingly studied. A direct interaction between COMMD1, a regulator of the Cu pathway, and hypoxia-inducible factor (HIF) HIF-1a does exist in ischemic injury, but little information has been collected on the role of Cu in hypoxia associated with AD thus far. The current review deals with this matter in an attempt to structurally discuss the link between miRNA expression and Cu dysregulation in AD and CVDs.
MeSH term(s)	Aged ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Cardiovascular Diseases/genetics ; Copper ; Humans ; Hypoxia ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Transcription Factors
Chemical Substances	MicroRNAs ; Transcription Factors ; Copper (789U1901C5)
Language	English
Publishing date	2022-03-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23063327
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Article: Incidence of young-onset dementia in Italy: The Brescia register study.

Alzheimer's & dementia (Amsterdam, Netherlands)

2024 Volume 16, Issue 1, Page(s) e12544

Abstract: Introduction: The goal of the present work was to assess the incidence of dementia with onset before the age of 65 years (i.e., young-onset dementia [YOD]) and define the frequencies of young-onset Alzheimer's disease (AD), frontotemporal lobar ... ...

Abstract	Introduction: The goal of the present work was to assess the incidence of dementia with onset before the age of 65 years (i.e., young-onset dementia [YOD]) and define the frequencies of young-onset Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), and dementia with Lewy bodies (DLB) in the general population. Methods: The study was conducted from January 1, 2019 to December 31, 2019 in Brescia province (population: 1,268,455). During the study period, all new YOD cases (incident YOD) were counted, and all patients' records reviewed. The incidence was standardized to the Italian general population in 2019. Results: A total of 29 YOD patients were diagnosed. The age-sex standardized incidence rate was 4.58 (95% confidence interval, 3.07-6.58) per 100,000 person-years. No difference in incidence rate between YOD due to AD or FTLD ( Discussion: Presenting neurodegenerative YOD phenotypes encompasses both AD and FTLD. Improved knowledge on YOD epidemiology is essential to adequately plan and organize health services.
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1002/dad2.12544
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Article: Loss of Neuroprotective Factors in Neurodegenerative Dementias: The End or the Starting Point?

Benussi, Luisa / Binetti, Giuliano / Ghidoni, Roberta

Frontiers in neuroscience

2017 Volume 11, Page(s) 672

Abstract: Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of ... ...

Abstract	Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of neuroprotective factors, across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD), Frontotemporal dementia (FTD) and Lewy body dementia (LBD). We will report evidences that the Brain Derived Neurotrophic Factor (BDNF), the most investigated and characterized brain neurotrophin, progranulin, a multi-functional adipokine with trophic and growth factor properties, and cystatin C, a neuroprotective growth factor, are reduced in AD, FTD, and LBD. Moreover, we will review the molecular mechanism underlying the loss of neuroprotective factors in neurodegenerative diseases leading to dementia, with a special focus on endo-lysosomal pathway and intercellular communication mediated by extracellular vesicles. Exploring the shared commonality of disease mechanisms is of pivotal importance to identify novel potential therapeutic targets and to develop treatments to delay, slow or block disease progression.
Language	English
Publishing date	2017-12-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2017.00672
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Article ; Online: Survival in Incident Cases with Frontotemporal Lobar Degeneration: A Registry-Based Study.

Borroni, Barbara / Urso, Daniele / Zecca, Chiara / Binetti, Giuliano / Fostinelli, Silvia / Benussi, Luisa / Ghidoni, Roberta / Tarantino, Barbara / Rivolta, Jasmine / Dell'Abate, Maria Teresa / Alberici, Antonella / Logroscino, Giancarlo

Journal of Alzheimer's disease : JAD

2023 Volume 96, Issue 3, Page(s) 1019–1024

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 ... ...

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.
MeSH term(s)	Humans ; Frontotemporal Lobar Degeneration/epidemiology ; Frontotemporal Lobar Degeneration/diagnosis ; Frontotemporal Dementia ; Registries
Language	English
Publishing date	2023-11-06
Publishing country	Netherlands
Document type	Letter ; 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-230676
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