A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors
Swift, Imogen J. (Queen Square)
Rademakers, Rosa (University of Antwerp)
Finch, NiCole (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Baker, Matt (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Ghidoni, Roberta (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
Benussi, Luisa (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
Binetti, Giuliano (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (Brescia, Itàlia))
Rossi, Giacomina (Fondazione IRCCS Istituto Neurologico Carlo Besta (Milà, Itàlia))
Synofzik, Matthis (German Center of Neurodegenerative Diseases (DZNE))
Wilke, Carlo (German Center of Neurodegenerative Diseases (DZNE))
Mengel, David (German Center of Neurodegenerative Diseases (DZNE))
Graff, Caroline (Karolinska University Hospital)
Takada, Leonel Tadao (University of São Paulo Medical School)
Sanchez-Valle, Raquel (Hospital Clínic i Provincial de Barcelona)
Antonell, Anna (Hospital Clínic i Provincial de Barcelona)
Galimberti, Daniela (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milà, Itàlia))
Fenoglio, Chiara (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milà, Itàlia))
Serpente, Maria (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milà, Itàlia))
Arcaro, Marina (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milà, Itàlia))
Schreiber, Stefanie (Otto Von Guericke University)
Vielhaber, Stefan (Otto Von Guericke University)
Arndt, Philipp (Otto Von Guericke University)
Santana, Isabel (University of Coimbra)
Almeida, Maria Rosário (University of Coimbra)
Moreno, Fermín (Biodonostia Health Research Insitute)
Barandiaran, Myriam (Biodonostia Health Research Insitute)
Gabilondo, Alazne (Biodonostia Health Research Insitute)
Stubert, Johannes (Rostock University Medical Center)
Gómez-Tortosa, Estrella (Hospital Universitario Fundación Jiménez Díaz)
Agüero, Pablo (Hospital Universitario Fundación Jiménez Díaz)
Sainz, M. José (Hospital Universitario Fundación Jiménez Díaz)
Gohda, Tomohito (Juntendo University)
Murakoshi, Maki (Juntendo University)
Kamei, Nozomu (Kure Medical Center and Chugoku Cancer Center)
Kittel-Schneider, Sarah (University Hospital Würzburg)
Reif, Andreas (University Hospital of Frankfurt (Alemanya))
Weigl, Johannes (Hospital in Tauberbischofsheim)
Jian, Jinlong (University of Pennsylvania)
Liu, Chuanju (Yale University School of Medicine)
Serrero, Ginette (University of Maryland Greenebaum Comprehensive Cancer Center)
Greither, Thomas (Martin Luther University Halle-Wittenberg)
Theil, Gerit (Martin Luther University Halle-Wittenberg)
Lohmann, Ebba (German Center for Neurodegenerative Diseases (DZNE))
Gazzina, Stefano (Azienda Ospedaliera Spedali Civili di Brescia (Brescia, Itàlia))
Bagnoli, Silvia (Università degli Studi di Firenze)
Coppola, Giovanni (University of California)
Bruni, Amalia (Regional Neurogenetic Centre. ASPCZ)
Quante, Mirja (Tuebingen University Hospital)
Kiess, Wieland (University of Leipzig)
Hiemisch, Andreas (University of Leipzig)
Jurkutat, Anne (University of Leipzig)
Block, Matthew S. (Mayo Clinic (Rochester, Estats Units d'Amèrica))
Carlson, Aaron M. (University of Colorado Anschutz Medical Campus)
Bråthen, Geir (Trondheim University Hospital (Trondheim, Noruega))
Sando, Sigrid Botne (Trondheim University Hospital (Trondheim, Noruega))
Grøntvedt, Gøril Rolfseng (Trondheim University Hospital (Trondheim, Noruega))
Lauridsen, Camilla (Trondheim University Hospital (Trondheim, Noruega))
Heslegrave, Amanda (University College London Institute of Neurology)
Heller, Carolin (University College London Institute of Neurology)
Abel, Emily (University College London Institute of Neurology)
Gómez-Núñez, Alba (Hospital Clínic i Provincial de Barcelona)
Puey, Roger (Hospital Clínic i Provincial de Barcelona)
Arighi, Andrea (Ospedale Maggiore Policlinico)
Rotondo, Enmanuela (Ospedale Maggiore Policlinico)
Jiskoot, Lize C. (Erasmus MC University Medical Center)
Meeter, Lieke H.H. (Erasmus MC University Medical Center)
Durães, João (Centro Hospitalar E Universitário de Coimbra)
Lima, Marisa (Centro Hospitalar E Universitário de Coimbra)
Tábuas-Pereira, Miguel (University of Coimbra)
Lemos, João (University of Coimbra)
Boeve, Bradley (Mayo Clinic (Rochester, Estats Units d'Amèrica))
Petersen, Ronald C. (Mayo Clinic (Rochester, Estats Units d'Amèrica))
Dickson, Dennis W. (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Graff-Radford, Neill R. (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Leber, Isabelle (Sorbonne UniversitéInserm)
Sellami, Leila (Centre de Référence Des Démences Rares Ou Précoces)
Lamari, Foudil (Hôpital Pitié-Salpêtière (París, França))
Clot, Fabienne (Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix)
Borroni, Barbara (University of Brescia)
Cantoni, Valentina (University of Brescia)
Rivolta, Jasmine (University of Brescia)
Lleó, Alberto (Institut de Recerca Sant Pau)
Fortea, Juan (Institut de Recerca Sant Pau)
Alcolea, Daniel (Institut de Recerca Sant Pau)
Illán-Gala, Ignacio (Institut de Recerca Sant Pau)
Andres-Cerezo, Lucie (Institute of Rheumatology)
Van Damme, Philip (Katholieke Universiteit te Leuven (1970-))
Clarimón, Jordi (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Steinacker, Petra (University Clinic Halle)
Feneberg, Emily (Klinikum Rechts Der Isar)
Otto, Markus (Martin-Luther University Halle-Wittenberg)
van der Ende, Emma L. (Erasmus MC University Medical Center)
van Swieten, John C. (Erasmus MC University Medical Center)
Seelaar, Harro (Erasmus MC University Medical Center)
Zetterberg, Henrik (Hong Kong Center for Neurodegenerative Diseases)
Sogorb-Esteve, Aitana (Queen Square)
Rohrer, Jonathan D. (Queen Square)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74. 8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3. 43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0. 007) with a trend in non-carriers (p = 0. 062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Frontotemporal dementia ; Progranulin
Publicat a:	Alzheimer's research & therapy, Vol. 16 Núm. 1 (december 2024) , p. 66, ISSN 1758-9193

DOI: 10.1186/s13195-024-01420-z
PMID: 38539243

13 p, 2.3 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
Articles > Articles de recerca
Articles > Articles publicats