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Article ; Online: Head-to-head comparison of [

Aguero, Cinthya / Dhaynaut, Maeva / Amaral, Ana C / Moon, S-H / Neelamegam, Ramesh / Scapellato, Margaret / Carazo-Casas, Carlos / Kumar, Sunny / El Fakhri, Georges / Johnson, Keith / Frosch, Matthew P / Normandin, Marc D / Gómez-Isla, Teresa

Acta neuropathologica

2024 Volume 147, Issue 1, Page(s) 25

Abstract: We and others have shown that [ ...

Abstract	We and others have shown that [
MeSH term(s)	Humans ; Neurodegenerative Diseases/pathology ; Melanins/metabolism ; Brain/pathology ; Tauopathies/pathology ; Monoamine Oxidase/metabolism ; DNA-Binding Proteins/metabolism ; tau Proteins/metabolism ; Positron-Emission Tomography/methods ; Alzheimer Disease/pathology ; Carbolines ; Isoquinolines ; Pyridines
Chemical Substances	PI-2620 ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB) ; MK-6240 ; Melanins ; Monoamine Oxidase (EC 1.4.3.4) ; DNA-Binding Proteins ; tau Proteins ; Carbolines ; Isoquinolines ; Pyridines
Language	English
Publishing date	2024-01-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-023-02672-z
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Article: Event-related potentials during sustained attention and memory tasks: Utility as biomarkers for mild cognitive impairment.

Waninger, Shani / Berka, Chris / Meghdadi, Amir / Karic, Marija S / Stevens, Kimberly / Aguero, Cinthya / Sitnikova, Tatiana / Salat, David H / Verma, Ajay

Alzheimer's & dementia (Amsterdam, Netherlands)

2018 Volume 10, Page(s) 452–460

Abstract: Introduction: The objective of the study is to validate attention and memory tasks that elicit event-related potentials (ERPs) for utility as sensitive biomarkers for early dementia.: Methods: A 3-choice vigilance task designed to evaluate sustained ... ...

Abstract	Introduction: The objective of the study is to validate attention and memory tasks that elicit event-related potentials (ERPs) for utility as sensitive biomarkers for early dementia. Methods: A 3-choice vigilance task designed to evaluate sustained attention and standard image recognition memory task designed to evaluate attention, encoding, and image recognition memory were administered with concurrent electroencephalography acquisition to elicit ERPs in mild cognitive impairment (MCI) and healthy cohorts. ERPs were averaged, and mean or maximum amplitude of components was measured and compared between and within cohorts. Results: There was significant suppression of the amplitude of the late positive potential in the MCI cohort compared with the healthy controls during 3-choice vigilance task, predominantly over occipital and right temporal-parietal region, and standard image recognition memory task over all regions. During standard image recognition memory task, diminished performance showed strong correlation with electroencephalography measurements. The old/new effects observed in the healthy controls cohort correlated with performance and were lost in MCI. Discussion: ERPs obtained during cognitive tasks may provide a powerful tool for assessing MCI and have strong potential as sensitive and robust biomarkers for tracking disease progression and evaluating response to investigative therapeutics.
Language	English
Publishing date	2018-07-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1016/j.dadm.2018.05.007
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Article ; Online: [

Marquié, Marta / Agüero, Cinthya / Amaral, Ana C / Villarejo-Galende, Alberto / Ramanan, Prianca / Chong, Michael Siao Tick / Sáez-Calveras, Nil / Bennett, Rachel E / Verwer, Eline E / Kim, Sally Ji Who / Dhaynaut, Maeva / Alvarez, Victor E / Johnson, Keith A / McKee, Ann C / Frosch, Matthew P / Gómez-Isla, Teresa

Acta neuropathologica communications

2019 Volume 7, Issue 1, Page(s) 164

Abstract: Introduction: Chronic traumatic encephalopathy (CTE) is a tauopathy associated to repetitive head trauma. There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron ... ...

Abstract	Introduction: Chronic traumatic encephalopathy (CTE) is a tauopathy associated to repetitive head trauma. There are no validated in vivo biomarkers of CTE and a definite diagnosis can only be made at autopsy. Recent studies have shown that positron emission tomography (PET) tracer AV-1451 (Flortaucipir) exhibits high binding affinity for paired helical filament (PHF)-tau aggregates in Alzheimer (AD) brains but relatively low affinity for tau lesions in other tauopathies like temporal lobal degeneration (FTLD)-tau, progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). Little is known, however, about the binding profile of this ligand to the tau-containing lesions of CTE. Objective: To study the binding properties of [ Methods: We performed [ Results: Despite the presence of abundant tau aggregates in multiple regions in all CTE brains, only faint or no [ Conclusion: AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in CTE. The existence of disease-specific tau conformations may likely explain the differential binding affinity of this tracer for tau lesions in different tauopathies.
MeSH term(s)	Aged ; Aged, 80 and over ; Brain/metabolism ; Brain/pathology ; Carbolines ; Chronic Traumatic Encephalopathy/complications ; Chronic Traumatic Encephalopathy/metabolism ; Chronic Traumatic Encephalopathy/pathology ; Female ; Humans ; Male ; Middle Aged ; Positron-Emission Tomography ; Tauopathies/complications ; Tauopathies/metabolism ; Tauopathies/pathology ; tau Proteins/analysis ; tau Proteins/metabolism
Chemical Substances	Carbolines ; MAPT protein, human ; tau Proteins ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB)
Language	English
Publishing date	2019-10-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-019-0808-1
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Article ; Online: Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue.

Aguero, Cinthya / Dhaynaut, Maeva / Normandin, Marc D / Amaral, Ana C / Guehl, Nicolas J / Neelamegam, Ramesh / Marquie, Marta / Johnson, Keith A / El Fakhri, Georges / Frosch, Matthew P / Gomez-Isla, Teresa

Acta neuropathologica communications

2019 Volume 7, Issue 1, Page(s) 37

Abstract: F-18]-MK-6240, a novel tau positron emission tomography (PET) tracer recently discovered for the in vivo detection of neurofibrillary tangles, has the potential to improve diagnostic accuracy in the detection of Alzheimer disease. We have examined ... ...

Abstract	[F-18]-MK-6240, a novel tau positron emission tomography (PET) tracer recently discovered for the in vivo detection of neurofibrillary tangles, has the potential to improve diagnostic accuracy in the detection of Alzheimer disease. We have examined regional and substrate-specific binding patterns as well as possible off-target binding of this tracer on human brain tissue to advance towards its validation. We applied [F-18]-MK-6240 phosphor screen and high resolution autoradiography to postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau (Pick's disease, progressive supranuclear palsy and corticobasal degeneration), chronic traumatic encephalopathy, frontotemporal lobar degeneration-Tar DNA-binding protein 43 (TDP-43), dementia with Lewy bodies, cerebral amyloid angiopathy and elderly controls free of pathologic changes of neurodegenerative disease. We also directly compared the binding properties of [F-18]-MK-6240 and [F-18]-AV-1451 in human tissue, and examined potential nonspecific binding of both tau tracers to monoamine oxidases (MAO) by using autoradiography in the presence of selective monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) inhibitors. Our data indicate that MK-6240 strongly binds to neurofibrillary tangles in Alzheimer disease but does not seem to bind to a significant extent to tau aggregates in non-Alzheimer tauopathies, suggesting that it may have a limited utility for the in vivo detection of these pathologies. There is no evidence of binding to lesions containing β-amyloid, α-synuclein or TDP-43. In addition, we identified MK-6240 strong off-target binding to neuromelanin and melanin-containing cells, and some weaker binding to areas of hemorrhage. These binding patterns are nearly identical to those previously reported by our group and others for [F-18]-AV-1451. Of note, [F-18]-MK-6240 and [F-18]-AV-1451 autoradiographic binding signals were only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline, suggesting that MAO enzymes do not appear to be a significant binding target of any of these two tracers. Together these novel findings provide relevant insights for the correct interpretation of in vivo [F-18]-MK-6240 PET imaging.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Autoradiography/methods ; Autoradiography/standards ; Brain/diagnostic imaging ; Brain/metabolism ; Brain/pathology ; Female ; Fluorine Radioisotopes/metabolism ; Fluorine Radioisotopes/standards ; Humans ; Isoquinolines/metabolism ; Isoquinolines/standards ; Male ; Middle Aged ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Positron-Emission Tomography/methods ; Positron-Emission Tomography/standards ; Radiopharmaceuticals/metabolism ; Radiopharmaceuticals/standards ; Reproducibility of Results
Chemical Substances	Fluorine Radioisotopes ; Isoquinolines ; MK-6240 ; Radiopharmaceuticals ; Fluorine-18 (GZ5I74KB8G)
Language	English
Publishing date	2019-03-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-019-0686-6
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Article: Cortical thickness across the lifespan in a Colombian cohort with autosomal-dominant Alzheimer's disease: A cross-sectional study.

Fox-Fuller, Joshua T / Torrico-Teave, Heirangi / d'Oleire Uquillas, Federico / Chen, Kewei / Su, Yi / Chen, Yinghua / Brickhouse, Michael / Sanchez, Justin S / Aguero, Cinthya / Jacobs, Heidi I L / Hampton, Olivia / Guzmán-Vélez, Edmarie / Vila-Castelar, Clara / Aguirre-Acevedo, Daniel C / Baena, Ana / Artola, Arabiye / Martinez, Jairo / Pluim, Celina F / Alvarez, Sergio /

Ochoa-Escudero, Martin / Reiman, Eric M / Sperling, Reisa A / Lopera, Francisco / Johnson, Keith A / Dickerson, Bradford C / Quiroz, Yakeel T

Alzheimer's & dementia (Amsterdam, Netherlands)

2021 Volume 13, Issue 1, Page(s) e12233

Abstract: Introduction: Cortical thinning is a marker of neurodegeneration in Alzheimer's disease (AD). We investigated the age-related trajectory of cortical thickness across the lifespan (9-59 years) in a Colombian kindred with autosomal dominant AD (ADAD).: ... ...

Abstract	Introduction: Cortical thinning is a marker of neurodegeneration in Alzheimer's disease (AD). We investigated the age-related trajectory of cortical thickness across the lifespan (9-59 years) in a Colombian kindred with autosomal dominant AD (ADAD). Methods: Two hundred eleven participants (105 presenilin-1 [ Results: Unimpaired carriers exhibited elevated cortical thickness compared to non-carriers, and thickness more negatively correlated with age and cognition in carriers relative to non-carriers. We found increased cortical thickness in child carriers, after which thickness steadied compared to non-carriers prior to a rapid reduction in the decade leading up to the expected age at cognitive impairment in carriers. Discussion: Findings suggest that cortical thickness may fluctuate across the ADAD lifespan, from early-life increased thickness to atrophy proximal to clinical onset.
Language	English
Publishing date	2021-09-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1002/dad2.12233
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Article ; Online: Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson's case.

Marquié, Marta / Verwer, Eline E / Meltzer, Avery C / Kim, Sally Ji Who / Agüero, Cinthya / Gonzalez, Jose / Makaretz, Sara J / Siao Tick Chong, Michael / Ramanan, Prianca / Amaral, Ana C / Normandin, Marc D / Vanderburg, Charles R / Gomperts, Stephen N / Johnson, Keith A / Frosch, Matthew P / Gómez-Isla, Teresa

Acta neuropathologica communications

2017 Volume 5, Issue 1, Page(s) 75

Abstract: F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD ... ...

Abstract	[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas. We and others have shown that [F-18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood products on postmortem material; and this is important for the correct interpretation of PET images. In the present study, we further investigated [F-18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson's disease (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the PD diagnosis. Phosphor screen and high resolution autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of neuromelanin-containing neurons in the substantia nigra, leptomeningeal melanocytes adjacent to ventricles and midbrain, and microhemorrhages in the occipital cortex (all reflecting off-target binding), in addition to incidental age-related neurofibrillary tangles in the entorhinal cortex. Additional legacy postmortem brain samples containing basal ganglia, choroid plexus, and parenchymal hemorrhages from 20 subjects with various neuropathologic diagnoses were also included in the autoradiography experiments to better understand what [F-18]-AV-1451 in vivo positivity in those regions means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the basal ganglia of the PD case or any of the other subjects. Off-target binding in postmortem choroid plexus samples was only observed in subjects harboring leptomeningeal melanocytes within the choroidal stroma. Off-target binding to parenchymal hemorrhages was noticed in postmortem material from subjects with cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for neurofibrillary tau pathology but also exhibits off-target binding to neuromelanin, melanin and blood components. The robust off-target in vivo retention in basal ganglia and choroid plexus, in the absence of tau deposits, meningeal melanocytes or any other identifiable binding substrate by autoradiography in the PD case reported here, also suggests that the PET signal in those regions may be influenced, at least in part, by biological or technical factors that occur in vivo and are not captured by autoradiography.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Autoradiography ; Brain/diagnostic imaging ; Brain/metabolism ; Brain Mapping ; Carbolines ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/metabolism ; Parkinson Disease/pathology ; Positron-Emission Tomography ; Radiopharmaceuticals
Chemical Substances	Carbolines ; Radiopharmaceuticals ; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole (J09QS3Z3WB)
Language	English
Publishing date	2017-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-017-0482-0
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Article ; Online: The impact of COVID-19 on the well-being and cognition of older adults living in the United States and Latin America.

Babulal, Ganesh M / Torres, Valeria L / Acosta, Daisy / Agüero, Cinthya / Aguilar-Navarro, Sara / Amariglio, Rebecca / Ussui, Juliana Aya / Baena, Ana / Bocanegra, Yamile / Brucki, Sonia Maria Dozzi / Bustin, Julian / Cabrera, Diego M / Custodio, Nilton / Diaz, Monica M / Peñailillo, Lissette Duque / Franco, Idalid / Gatchel, Jennifer R / Garza-Naveda, Ana Paola / González Lara, Mariana /

Gutiérrez-Gutiérrez, Lidia / Guzmán-Vélez, Edmarie / Hanseeuw, Bernard J / Jimenez-Velazquez, Ivonne Z / Rodríguez, Tomás León / Llibre-Guerra, Jorge / Marquine, María J / Martinez, Jairo / Medina, Luis D / Miranda-Castillo, Claudia / Morlett Paredes, Alejandra / Munera, Diana / Nuñez-Herrera, Alberto / de Oliveira, Maira Okada / Palmer-Cancel, Santiago J / Pardilla-Delgado, Enmanuelle / Perales-Puchalt, Jaime / Pluim, Celina / Ramirez-Gomez, Liliana / Rentz, Dorene M / Rivera-Fernández, Claudia / Rosselli, Monica / Serrano, Cecilia M / Suing-Ortega, Maria Jose / Slachevsky, Andrea / Soto-Añari, Marcio / Sperling, Reisa A / Torrente, Fernando / Thumala, Daniela / Vannini, Patrizia / Vila-Castelar, Clara / Yañez-Escalante, Tatiana / Quiroz, Yakeel T

EClinicalMedicine

2021 Volume 35, Page(s) 100848

Abstract: Background: In the COVID-19 pandemic, older adults from vulnerable ethnoracial groups are at high risk of infection, hospitalization, and death. We aimed to explore the pandemic's impact on the well-being and cognition of older adults living in the ... ...

Abstract	Background: In the COVID-19 pandemic, older adults from vulnerable ethnoracial groups are at high risk of infection, hospitalization, and death. We aimed to explore the pandemic's impact on the well-being and cognition of older adults living in the United States (US), Argentina, Chile, Mexico, and Peru. Methods: 1,608 (646 White, 852 Latino, 77 Black, 33 Asian; 72% female) individuals from the US and four Latin American countries aged ≥ 55 years completed an online survey regarding well-being and cognition during the pandemic between May and September 2020. Outcome variables (pandemic impact, discrimination, loneliness, purpose of life, subjective cognitive concerns) were compared across four US ethnoracial groups and older adults living in Argentina, Chile, Mexico, and Peru. Findings: Mean age for all participants was 66.7 ( Interpretation: The COVID-19 pandemic has differentially impacted the well-being of older ethnically diverse individuals in the US and Latin America. Future studies should examine how mediators like income and coping skills modify the pandemic's impact. Funding: Massachusetts General Hospital Department of Psychiatry.
Language	English
Publishing date	2021-04-27
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2021.100848
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Article ; Online: The impact of COVID-19 on the well-being and cognition of older adults living in the United States and Latin America

Ganesh M. Babulal / Valeria L. Torres / Daisy Acosta / Cinthya Agüero / Sara Aguilar-Navarro / Rebecca Amariglio / Juliana Aya Ussui / Ana Baena / Yamile Bocanegra / Sonia Maria Dozzi Brucki / Julian Bustin / Diego M. Cabrera / Nilton Custodio / Monica M. Diaz / Lissette Duque Peñailillo / Idalid Franco / Jennifer R. Gatchel / Ana Paola Garza-Naveda / Mariana González Lara /

Lidia Gutiérrez-Gutiérrez / Edmarie Guzmán-Vélez / Bernard J. Hanseeuw / Ivonne Z. Jimenez-Velazquez / Tomás León Rodríguez / Jorge Llibre-Guerra / María J. Marquine / Jairo Martinez / Luis D. Medina / Claudia Miranda-Castillo / Alejandra Morlett Paredes / Diana Munera / Alberto Nuñez-Herrera / Maira Okada de Oliveira / Santiago J. Palmer-Cancel / Enmanuelle Pardilla-Delgado / Jaime Perales-Puchalt / Celina Pluim / Liliana Ramirez-Gomez / Dorene M. Rentz / Claudia Rivera-Fernández / Monica Rosselli / Cecilia M Serrano / Maria Jose Suing-Ortega / Andrea Slachevsky / Marcio Soto-Añari / Reisa A. Sperling / Fernando Torrente / Daniela Thumala / Patrizia Vannini / Clara Vila-Castelar

EClinicalMedicine, Vol 35, Iss , Pp 100848- (2021)

2021

Abstract	Background: In the COVID-19 pandemic, older adults from vulnerable ethnoracial groups are at high risk of infection, hospitalization, and death. We aimed to explore the pandemic's impact on the well-being and cognition of older adults living in the United States (US), Argentina, Chile, Mexico, and Peru. Methods: 1,608 (646 White, 852 Latino, 77 Black, 33 Asian; 72% female) individuals from the US and four Latin American countries aged ≥ 55 years completed an online survey regarding well-being and cognition during the pandemic between May and September 2020. Outcome variables (pandemic impact, discrimination, loneliness, purpose of life, subjective cognitive concerns) were compared across four US ethnoracial groups and older adults living in Argentina, Chile, Mexico, and Peru. Findings: Mean age for all participants was 66.7 (SD = 7.7) years and mean education was 15.4 (SD = 2.7) years. Compared to Whites, Latinos living in the US reported greater economic impact (p < .001, ηp2 = 0.031); while Blacks reported experiencing discrimination more often (p < .001, ηp2 = 0.050). Blacks and Latinos reported more positive coping (p < .001, ηp2 = 0.040). Compared to Latinos living in the US, Latinos in Chile, Mexico, and Peru reported greater pandemic impact, Latinos in Mexico and Peru reported more positive coping, Latinos in Argentina, Mexico, and Peru had greater economic impact, and Latinos in Argentina, Chile, and Peru reported less discrimination. Interpretation: The COVID-19 pandemic has differentially impacted the well-being of older ethnically diverse individuals in the US and Latin America. Future studies should examine how mediators like income and coping skills modify the pandemic's impact. Funding: Massachusetts General Hospital Department of Psychiatry.
Keywords	COVID-19 ; US ; Latin America ; Diversity ; Well-being ; Cognition ; Medicine (General) ; R5-920
Subject code	306
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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