Fluid Biomarkers in Individuals at Risk for Genetic Prion Disease up to Disease Conversion.

Humans Female Male Middle Aged Biomarkers / cerebrospinal fluid Prion Proteins / genetics Prion Diseases / genetics Longitudinal Studies Adult tau Proteins / cerebrospinal fluid Neurofilament Proteins / cerebrospinal fluid Heterozygote Glial Fibrillary Acidic Protein / blood Disease Progression alpha-Synuclein / cerebrospinal fluid

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
23 Jul 2024
Historique:
medline: 19 6 2024
pubmed: 19 6 2024
entrez: 19 6 2024
Statut: ppublish

Résumé

To longitudinally characterize disease-relevant CSF and plasma biomarkers in individuals at risk for genetic prion disease up to disease conversion. This single-center longitudinal cohort study has followed known carriers of Among 41 carriers and 21 controls enrolled, 28 (68%) and 15 (71%) were female, and mean ages were 47.5 and 46.1. At baseline, all individuals were asymptomatic. We observed RT-QuIC seeding activity in the CSF of 3 asymptomatic E200K carriers who subsequently converted to symptomatic and died of prion disease. 1 P102L carrier remained RT-QuIC negative through symptom conversion. No other individuals developed symptoms. The prodromal window from detection of RT-QuIC positivity to disease onset was 1 year long in an E200K individual homozygous (V/V) at PRNP codon 129 and 2.5 and 3.1 years in 2 codon 129 heterozygotes (M/V). Changes in neurodegenerative and neuroinflammatory markers were variably observed prior to onset, with increases observed for plasma NfL in 4/4 converters, and plasma GFAP, CSF NfL, CSF T-tau, and CSF beta-synuclein each in 2/4 converters, although values relative to age and fold changes relative to individual baseline were not remarkable for any of these markers. CSF PrP was longitudinally stable with mean coefficient of variation 9.0% across all individuals over up to 6 years, including data from converting individuals at RT-QuIC-positive timepoints. CSF prion seeding activity may represent the earliest detectable prodromal sign in E200K carriers. Neuronal damage and neuroinflammation markers show limited sensitivity in the prodromal phase. CSF PrP levels remain stable even in the presence of RT-QuIC seeding activity. ClinicalTrials.gov NCT05124392 posted 2017-12-01, updated 2023-01-27.

Identifiants

DOI: 10.1212/WNL.0000000000209506 PMID: 38896810
pubmed: 38896810
doi: 10.1212/WNL.0000000000209506
doi:

Substances chimiques

Biomarkers 0
Prion Proteins 0
PRNP protein, human 0
neurofilament protein L 0
tau Proteins 0
Neurofilament Proteins 0
Glial Fibrillary Acidic Protein 0
alpha-Synuclein 0
GFAP protein, human 0

Banques de données

ClinicalTrials.gov
['NCT05124392']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e209506

Auteurs

Sonia M Vallabh (SM)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
ORCID: 0000-0003-3824-2702

Meredith A Mortberg (MA)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Shona W Allen (SW)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Ashley C Kupferschmid (AC)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Pia Kivisakk (P)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Bruno L Hammerschlag (BL)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Anna Bolling (A)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Bianca A Trombetta (BA)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Kelli Devitte-McKee (K)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Abaigeal M Ford (AM)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Lauren E Sather (LE)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Griffin Duffy (G)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Ashley Rivera (A)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Jessica Gerber (J)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Alison J McManus (AJ)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.

Eric V Minikel (EV)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
ORCID: 0000-0003-2206-1608

Steven E Arnold (SE)

From the McCance Center for Brain Health (S.M.V., M.A.M., E.V.M.) and Department of Neurology (S.M.V., M.A.M., S.W.A., A.C.K., P.K., B.L.H., A.B., B.A.T., K.D.-M., A.M.F., L.E.S., G.D., A.R., J.G., A.J.M., E.V.M., S.E.A.), Massachusetts General Hospital, Boston; Stanley Center for Psychiatric Research (S.M.V., M.A.M., E.V.M.), Broad Institute of MIT and Harvard, Cambridge; and Department of Neurology (S.M.V., P.K., E.V.M., S.E.A.), Harvard Medical School, Boston, MA.
ORCID: 0000-0002-9487-415X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Prions › Protéines prion › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladies à prions › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études longitudinales › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines neurofilamenteuses › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Hétérozygote › Fluid Biomarkers in Individuals at Risk for...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines de filaments intermédiaires › Protéine gliofibrillaire acide › Fluid Biomarkers in Individuals at Risk for...
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