CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder

We investigated the biomarker profile of neurodegeneration, Alzheimer's and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We...

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Authors: Muñoz Lopetegi, Amaia, Baiardi, Simone, Balasa, Mircea, Mammana, Angela, Mayà Casalprim, Gerard, Rossi, Marcello, Serradell, Mónica, Zenesini, Corrado, Ticca, Alice, Santamaria Cano, Joan, Dellavalle, Sofia, Gaig Ventura, Carles, Iranzo, Alex, Parchi, Piero
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/219476
Online Access:https://hdl.handle.net/2445/219476
Access Level:Open access
Keyword:Malaltia d'Alzheimer
Demència amb cossos de Lewy
Trastorns del son
Alzheimer's disease
Lewy body dementia
Sleep disorders
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spelling CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorderMuñoz Lopetegi, AmaiaBaiardi, SimoneBalasa, MirceaMammana, AngelaMayà Casalprim, GerardRossi, MarcelloSerradell, MónicaZenesini, CorradoTicca, AliceSantamaria Cano, JoanDellavalle, SofiaGaig Ventura, CarlesIranzo, AlexParchi, PieroMalaltia d'AlzheimerDemència amb cossos de LewyTrastorns del sonAlzheimer's diseaseLewy body dementiaSleep disordersWe investigated the biomarker profile of neurodegeneration, Alzheimer's and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We assessed misfolded α-synuclein (AS) by RT-QuIC assay, amyloid-beta peptides (Aβ42 and Aβ40), phosphorylated tau (p-tau), and total tau (t-tau) by CLEIA and neurofilament light chain (NfL) by ELISA. We detected AS in 75.3% of patients, pathologically decreased Aβ42/Aβ40 ratio in 22.5%, increased p-tau in 15.5%, increased t-tau in 14.9%, and elevated NfL in 14.7%. After a mean follow-up of 2.48 ± 2.75 years, 47 (38.1%) patients developed PD (n = 24) or DLB (n = 23). At CSF collection, AS positivity [HR 4.05 (1.26-12.99), p = 0.019], mild cognitive impairment [3.86 (1.96-7.61), p < 0.001], and abnormal DAT-SPECT [2.31 (1.09-4.91), p < 0.030] were independent predictors of conversion to PD and DLB. Among the other CSF markers, only elevated p-tau/Aβ42 was predictive of conversion, although only to DLB and not as an independent variable. In IRBD, CSF AS assessment by RT-QuIC provides an added value in defining the risk of short-term conversion to PD and DLB independent of clinical and instrumental investigations. Positive Alzheimer's disease (AD) pathology markers and elevated NfL occur in a subgroup of patients, but p-tau/Aβ42 is the only marker that predicts short-term conversion to DLB. Longer follow-up is needed to assess if AD biomarkers predict the later development of PD and DLB in IRBD.Springer Nature2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/219476Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41531-024-00770-7npj Parkinson's Disease, 2024, vol. 10, num.1https://doi.org/10.1038/s41531-024-00770-7cc-by (c) Muñoz-Lopetegi, A. et al., 2024http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2194762026-05-27T06:46:51Z
dc.title.none.fl_str_mv CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
title CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
spellingShingle CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
Muñoz Lopetegi, Amaia
Malaltia d'Alzheimer
Demència amb cossos de Lewy
Trastorns del son
Alzheimer's disease
Lewy body dementia
Sleep disorders
title_short CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
title_full CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
title_fullStr CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
title_full_unstemmed CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
title_sort CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder
dc.creator.none.fl_str_mv Muñoz Lopetegi, Amaia
Baiardi, Simone
Balasa, Mircea
Mammana, Angela
Mayà Casalprim, Gerard
Rossi, Marcello
Serradell, Mónica
Zenesini, Corrado
Ticca, Alice
Santamaria Cano, Joan
Dellavalle, Sofia
Gaig Ventura, Carles
Iranzo, Alex
Parchi, Piero
author Muñoz Lopetegi, Amaia
author_facet Muñoz Lopetegi, Amaia
Baiardi, Simone
Balasa, Mircea
Mammana, Angela
Mayà Casalprim, Gerard
Rossi, Marcello
Serradell, Mónica
Zenesini, Corrado
Ticca, Alice
Santamaria Cano, Joan
Dellavalle, Sofia
Gaig Ventura, Carles
Iranzo, Alex
Parchi, Piero
author_role author
author2 Baiardi, Simone
Balasa, Mircea
Mammana, Angela
Mayà Casalprim, Gerard
Rossi, Marcello
Serradell, Mónica
Zenesini, Corrado
Ticca, Alice
Santamaria Cano, Joan
Dellavalle, Sofia
Gaig Ventura, Carles
Iranzo, Alex
Parchi, Piero
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Demència amb cossos de Lewy
Trastorns del son
Alzheimer's disease
Lewy body dementia
Sleep disorders
topic Malaltia d'Alzheimer
Demència amb cossos de Lewy
Trastorns del son
Alzheimer's disease
Lewy body dementia
Sleep disorders
description We investigated the biomarker profile of neurodegeneration, Alzheimer's and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We assessed misfolded α-synuclein (AS) by RT-QuIC assay, amyloid-beta peptides (Aβ42 and Aβ40), phosphorylated tau (p-tau), and total tau (t-tau) by CLEIA and neurofilament light chain (NfL) by ELISA. We detected AS in 75.3% of patients, pathologically decreased Aβ42/Aβ40 ratio in 22.5%, increased p-tau in 15.5%, increased t-tau in 14.9%, and elevated NfL in 14.7%. After a mean follow-up of 2.48 ± 2.75 years, 47 (38.1%) patients developed PD (n = 24) or DLB (n = 23). At CSF collection, AS positivity [HR 4.05 (1.26-12.99), p = 0.019], mild cognitive impairment [3.86 (1.96-7.61), p < 0.001], and abnormal DAT-SPECT [2.31 (1.09-4.91), p < 0.030] were independent predictors of conversion to PD and DLB. Among the other CSF markers, only elevated p-tau/Aβ42 was predictive of conversion, although only to DLB and not as an independent variable. In IRBD, CSF AS assessment by RT-QuIC provides an added value in defining the risk of short-term conversion to PD and DLB independent of clinical and instrumental investigations. Positive Alzheimer's disease (AD) pathology markers and elevated NfL occur in a subgroup of patients, but p-tau/Aβ42 is the only marker that predicts short-term conversion to DLB. Longer follow-up is needed to assess if AD biomarkers predict the later development of PD and DLB in IRBD.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/219476
url https://hdl.handle.net/2445/219476
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41531-024-00770-7
npj Parkinson's Disease, 2024, vol. 10, num.1
https://doi.org/10.1038/s41531-024-00770-7
dc.rights.none.fl_str_mv cc-by (c) Muñoz-Lopetegi, A. et al., 2024
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Muñoz-Lopetegi, A. et al., 2024
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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