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Article ; Online: Correlations between the NMR Lipoprotein Profile,

de Rojas, Itziar / Del Barrio, Laura / Hernández, Isabel / Montrreal, Laura / García-González, Pablo / Marquié, Marta / Valero, Sergi / Cano, Amanda / Orellana, Adelina / Boada, Mercè / Mañes, Santos / Ruiz, Agustín

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer's disease. The inactivation of ... ...

Abstract	Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer's disease. The inactivation of the
MeSH term(s)	Animals ; Mice ; Humans ; Male ; Adult ; Aged ; Cholesterol ; Magnetic Resonance Spectroscopy ; Fasting ; Genotype ; Apolipoproteins E/genetics ; Cholesterol, HDL
Chemical Substances	Cholesterol (97C5T2UQ7J) ; Apolipoproteins E ; Cholesterol, HDL
Language	English
Publishing date	2023-01-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032186
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Article ; Online: Unveiling the sound of the cognitive status: Machine Learning-based speech analysis in the Alzheimer's disease spectrum.

Alzheimer's research & therapy

2024 Volume 16, Issue 1, Page(s) 26

Abstract: Background: Advancement in screening tools accessible to the general population for the early detection of Alzheimer's disease (AD) and prediction of its progression is essential for achieving timely therapeutic interventions and conducting ... ...

Abstract	Background: Advancement in screening tools accessible to the general population for the early detection of Alzheimer's disease (AD) and prediction of its progression is essential for achieving timely therapeutic interventions and conducting decentralized clinical trials. This study delves into the application of Machine Learning (ML) techniques by leveraging paralinguistic features extracted directly from a brief spontaneous speech (SS) protocol. We aimed to explore the capability of ML techniques to discriminate between different degrees of cognitive impairment based on SS. Furthermore, for the first time, this study investigates the relationship between paralinguistic features from SS and cognitive function within the AD spectrum. Methods: Physical-acoustic features were extracted from voice recordings of patients evaluated in a memory unit who underwent a SS protocol. We implemented several ML models evaluated via cross-validation to identify individuals without cognitive impairment (subjective cognitive decline, SCD), with mild cognitive impairment (MCI), and with dementia due to AD (ADD). In addition, we established models capable of predicting cognitive domain performance based on a comprehensive neuropsychological battery from Fundació Ace (NBACE) using SS-derived information. Results: The results of this study showed that, based on a paralinguistic analysis of sound, it is possible to identify individuals with ADD (F1 = 0.92) and MCI (F1 = 0.84). Furthermore, our models, based on physical acoustic information, exhibited correlations greater than 0.5 for predicting the cognitive domains of attention, memory, executive functions, language, and visuospatial ability. Conclusions: In this study, we show the potential of a brief and cost-effective SS protocol in distinguishing between different degrees of cognitive impairment and forecasting performance in cognitive domains commonly affected within the AD spectrum. Our results demonstrate a high correspondence with protocols traditionally used to assess cognitive function. Overall, it opens up novel prospects for developing screening tools and remote disease monitoring.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Alzheimer Disease/psychology ; Speech ; Neuropsychological Tests ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Cognition ; Machine Learning ; Disease Progression
Language	English
Publishing date	2024-02-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/s13195-024-01394-y
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Article: Mitochondrial DNA and Alzheimer’s disease: a first case–control study of the Tunisian population

Ben Salem, Nesrine / Boussetta, Sami / de Rojas, Itziar / Moreno-Grau, Sonia / Montrreal, Laura / Mokni, Narjes / Mahmoud, Imene / Younes, Samia / Daouassi, Nizar / Frih-Ayed, Mahbouba / Hammami, Afef / Ben Ammar Elgaaied, Amel / Ruiz, Agustín / Cherni, Lotfi

Molecular biology reports. 2022 Mar., v. 49, no. 3

2022

Abstract: BACKGROUND: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial ... ...

Abstract	BACKGROUND: Alzheimer’s disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial alteration has been proposed as a possible cause of AD. Therefore, several studies have focused on finding an association between inherited mitochondrial DNA variants and AD onset. METHODS: In this study, we looked, for the first time, for a potential association between mitochondrial haplogroups or polymorphisms and AD in the Tunisian population. We also evaluated the distribution of the major genetic risk factor for AD, the apolipoprotein E epsilon 4 (APOE ε4), in this population. In total, 159 single-nucleotide polymorphisms (SNPs) of mitochondrial DNA haplogroups were genotyped in 254 individuals (58 patients and 196 controls). An additional genotyping of APOE ε4 was performed. RESULTS: No significant association between mitochondrial haplogroups and AD was found. However, two individual SNPs, A5656G (p = 0.03821, OR = 10.46) and A13759G (p = 0.03719, OR = 10.78), showed a significant association with AD. APOE 4 was confirmed as a risk factor for AD (p = 0.000014). CONCLUSION: Our findings may confirm the absence of a relation between mitochondrial haplogroups and AD and support the possible involvement of some inherited variants in the pathogenicity of AD.
Keywords	apolipoprotein E ; case-control studies ; etiology ; genotyping ; mitochondria ; mitochondrial DNA ; molecular biology ; neurodegenerative diseases ; pathogenicity ; risk factors
Language	English
Dates of publication	2022-03
Size	p. 1687-1700.
Publishing place	Springer Netherlands
Document type	Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06978-7
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Article: Harnessing acoustic speech parameters to decipher amyloid status in individuals with mild cognitive impairment.

Frontiers in neuroscience

2023 Volume 17, Page(s) 1221401

Abstract: Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive functions. Currently, there are no effective treatments for AD, underscoring the importance of identifying individuals in the preclinical stages of ... ...

Abstract	Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive functions. Currently, there are no effective treatments for AD, underscoring the importance of identifying individuals in the preclinical stages of mild cognitive impairment (MCI) to enable early interventions. Among the neuropathological events associated with the onset of the disease is the accumulation of amyloid protein in the brain, which correlates with decreased levels of A
Language	English
Publishing date	2023-09-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1221401
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Article ; Online: Mitochondrial DNA and Alzheimer's disease: a first case-control study of the Tunisian population.

Molecular biology reports

2021 Volume 49, Issue 3, Page(s) 1687–1700

Abstract: Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial ... ...

Abstract	Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder in humans and presents a major health problem throughout the world. The etiology of AD is complex, and many factors are implicated, including mitochondria. Mitochondrial alteration has been proposed as a possible cause of AD. Therefore, several studies have focused on finding an association between inherited mitochondrial DNA variants and AD onset. Methods: In this study, we looked, for the first time, for a potential association between mitochondrial haplogroups or polymorphisms and AD in the Tunisian population. We also evaluated the distribution of the major genetic risk factor for AD, the apolipoprotein E epsilon 4 (APOE ε4), in this population. In total, 159 single-nucleotide polymorphisms (SNPs) of mitochondrial DNA haplogroups were genotyped in 254 individuals (58 patients and 196 controls). An additional genotyping of APOE ε4 was performed. Results: No significant association between mitochondrial haplogroups and AD was found. However, two individual SNPs, A5656G (p = 0.03821, OR = 10.46) and A13759G (p = 0.03719, OR = 10.78), showed a significant association with AD. APOE 4 was confirmed as a risk factor for AD (p = 0.000014). Conclusion: Our findings may confirm the absence of a relation between mitochondrial haplogroups and AD and support the possible involvement of some inherited variants in the pathogenicity of AD.
MeSH term(s)	Alleles ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Case-Control Studies ; DNA, Mitochondrial/genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Mitochondria/genetics ; Polymorphism, Single Nucleotide/genetics ; Tunisia/epidemiology
Chemical Substances	Apolipoprotein E4 ; Apolipoproteins E ; DNA, Mitochondrial
Language	English
Publishing date	2021-12-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06978-7
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Article ; Online: Establishing In-House Cutoffs of CSF Alzheimer's Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort.

International journal of molecular sciences

2022 Volume 23, Issue 13

Abstract: Background: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the ...

Abstract	Background: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing-Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland-Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan-Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates ( Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/psychology ; Amyloid beta-Peptides ; Biomarkers ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/psychology ; Cross-Sectional Studies ; Disease Progression ; Humans ; Peptide Fragments ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; Peptide Fragments ; tau Proteins
Language	English
Publishing date	2022-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23136891
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Article ; Online: Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.

Cano, Amanda / Esteban-de-Antonio, Ester / Bernuz, Mireia / Puerta, Raquel / García-González, Pablo / de Rojas, Itziar / Olivé, Claudia / Pérez-Cordón, Alba / Montrreal, Laura / Núñez-Llaves, Raúl / Sotolongo-Grau, Óscar / Alarcón-Martín, Emilio / Valero, Sergi / Alegret, Montserrat / Martín, Elvira / Martino-Adami, Pamela V / Ettcheto, Miren / Camins, Antonio / Vivas, Assumpta /

Gomez-Chiari, Marta / Tejero, Miguel Ángel / Orellana, Adelina / Tárraga, Lluís / Marquié, Marta / Ramírez, Alfredo / Martí, Mercè / Pividori, María Isabel / Boada, Mercè / Ruíz, Agustín

Journal of nanobiotechnology

2023 Volume 21, Issue 1, Page(s) 54

Abstract: In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive ... ...

Abstract	In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink
MeSH term(s)	Humans ; Amyloid beta-Peptides ; Cross-Sectional Studies ; Alzheimer Disease/metabolism ; Cognitive Dysfunction/diagnosis ; tau Proteins/cerebrospinal fluid ; Extracellular Vesicles/metabolism ; Biomarkers ; Peptide Fragments
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Biomarkers ; Peptide Fragments
Language	English
Publishing date	2023-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2100022-0
ISSN	1477-3155 ; 1477-3155
ISSN (online)	1477-3155
ISSN	1477-3155
DOI	10.1186/s12951-023-01793-7
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Article: Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment: The NORFACE cohort.

Marquié, Marta / García-Sánchez, Ainhoa / Alarcón-Martín, Emilio / Martínez, Joan / Castilla-Martí, Miguel / Castilla-Martí, Luis / Orellana, Adelina / Montrreal, Laura / de Rojas, Itziar / García-González, Pablo / Puerta, Raquel / Olivé, Clàudia / Cano, Amanda / Hernández, Isabel / Rosende-Roca, Maitée / Vargas, Liliana / Tartari, Juan Pablo / Esteban-De Antonio, Ester / Bojaryn, Urszula /

Ricciardi, Mario / Ariton, Diana M / Pytel, Vanesa / Alegret, Montserrat / Ortega, Gemma / Espinosa, Ana / Pérez-Cordón, Alba / Sanabria, Ángela / Muñoz, Nathalia / Lleonart, Núria / Aguilera, Núria / Tárraga, Lluís / Valero, Sergi / Ruiz, Agustín / Boada, Mercè

Frontiers in neuroscience

2023 Volume 17, Page(s) 1076177

Abstract: Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is ... ...

Abstract	Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aβ1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI). Materials and methods: Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, Results: The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, Discussion: Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort.
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1076177
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Article ; Online: The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment.

Marquié, Marta / García-Gutiérrez, Fernando / Orellana, Adelina / Montrreal, Laura / de Rojas, Itziar / García-González, Pablo / Puerta, Raquel / Olivé, Clàudia / Cano, Amanda / Hernández, Isabel / Rosende-Roca, Maitée / Vargas, Liliana / Tartari, Juan Pablo / Esteban-De Antonio, Ester / Bojaryn, Urszula / Ricciardi, Mario / Ariton, Diana M / Pytel, Vanesa / Alegret, Montserrat /

Ortega, Gemma / Espinosa, Ana / Pérez-Cordón, Alba / Sanabria, Ángela / Muñoz, Nathalia / Lleonart, Núria / Aguilera, Núria / García-Sánchez, Ainhoa / Alarcón-Martín, Emilio / Tárraga, Lluís / Ruiz, Agustín / Boada, Mercè / Valero, Sergi

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of ... ...

Abstract	Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.
MeSH term(s)	Humans ; Follow-Up Studies ; Depression/complications ; Alzheimer Disease/pathology ; Cognitive Dysfunction/pathology ; Amyloidosis/complications ; Biomarkers/cerebrospinal fluid ; Disease Progression ; Neuropsychological Tests ; Amyloid beta-Peptides/cerebrospinal fluid
Chemical Substances	Biomarkers ; Amyloid beta-Peptides
Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24021371
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Article ; Online: Author Correction: Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic.

Valero, Sergi / Marquié, Marta / De Rojas, Itziar / Espinosa, Ana / Moreno-Grau, Sonia / Orellana, Adelina / Montrreal, Laura / Hernández, Isabel / Mauleón, Ana / Rosende-Roca, Maiteé / Alegret, Montse / Pérez-Cordón, Alba / Ortega, Gemma / Roberto, Natalia / Sanabria, Angela / Abdelnour, Carla / Gil, Silvia / Tartari, Juan Pablo / Vargas, Liliana /

Antonio, Ester Esteban-De / Benaque, Alba / Tárraga, Lluís / Boada, Mercè / Ruíz, Agustín

Scientific reports

2021 Volume 11, Issue 1, Page(s) 4762

Language	English
Publishing date	2021-02-22
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-84389-1
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