Soluble SORL1 in cerebrospinal fluid as a marker for functional
impact of rare SORL1 variants

J 2026

Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants

DE WAAL MATTHIJS W, J.; J. VAN DER LEE SVEN; Melanie LUNDING; Lynn BOONKAMP; Nolan BARRETT et al.

Základní údaje

Originální název

Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants

Autoři

Vydání

ALZHEIMERS & DEMENTIA, Hoboken, WILEY, 2026, 1552-5260

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30103 Neurosciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 11.100 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Alzheimer's Disease; cerebrospinal fluid (CSF); missense variants; quantitative immunoassay; soluble SORL1 (sSORL1); SORL1

Štítky

14110517, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 7. 4. 2026 13:19, Mgr. Tereza Miškechová

Anotace

V originále

INTRODUCTION: The sortilin-related receptor (SORL1) directs APP and A beta trafficking within the retromer pathway. Cleavage at the cell surface releases soluble SORL1 (sSORL1) into cerebrospinal fluid (CSF). We examined whether CSF-sSORL1 can serve as an in vivo marker of genetically impaired SORL1. METHODS: CSF-sSORL1 was quantified by enzyme-linked immunosorbent assay (ELISA) in 218 participants: 90 carriers of SORL1 variants, 78 SORL1-wildtype (WT) AD patients, and 50 SORL1-WT controls. RESULTS: sSORL1 concentrations were significantly lower in carriers of protein-truncating and damaging missense variants. In SORL1-WT patients, CSF-sSORL1 correlated with pTau181 but not with A beta 42 among AD patients, and did not differ between patients and controls. DISCUSSION: These findings suggest that impaired SORL1 trafficking reduces receptor delivery to the cell surface and thereby decreases sSORL1 shedding, supporting its potential use as a pathway-specific biomarker.

Návaznosti

LX22NPO5107, projekt VaV

Název: Národní ústav pro neurologický výzkum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro neurologický výzkum, 5.1 EXCELES

NU22J-08-00075, projekt VaV

Název: Sledování funkce proteinu SORLA u pacientů s Alzheimerovou chorobou s časným nástupem

Investor: Ministerstvo zdravotnictví ČR, Sledování funkce proteinu SORLA u pacientů s Alzheimerovou chorobou s časným nástupem, Podprogram 2 - juniorský - výzkumníci do 35 let

8F20009, projekt VaV

Název: Identifying and treating SORL1-associated Alzheimer’s disease (Akronym: SORLA - FIX)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Pathogenic SORL1 variants in Alzheimer’s disease, Neurodegenerativní onemocnění (JPND)

Citovat

DE WAAL MATTHIJS W, J.; J. VAN DER LEE SVEN; Melanie LUNDING; Lynn BOONKAMP; Nolan BARRETT; Giulia MONTI; Anne Mette G JENSEN; Christian B VAEGTER; Jan RAŠKA; Soňa CESNÁRIKOVÁ; Jiří SEDMÍK; Calvin TRIEU; Marjan M WEISS; Van Spaendonk ROSALINA; Lisa VERMUNT; Georgii OZHEGOV; Niccolo TESI; Marc HULSMAN; Dovile JANULIENE; Arne MOLLER; Dáša BOHAČIAKOVÁ; M. VAN DER FLIER WIESJE; Olav M ANDERSEN; Charlotte E TEUNISSEN a Henne HOLSTEGE. Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants. ALZHEIMERS & DEMENTIA. Hoboken: WILEY, 2026, roč. 22, č. 2, s. 1-14. ISSN 1552-5260. Dostupné z: https://doi.org/10.1002/alz.71042.

@article{2565351,
   author = {De Waal Matthijs W, J. and Van Der Lee Sven, J. and Lunding, Melanie and Boonkamp, Lynn and Barrett, Nolan and Monti, Giulia and Jensen, Anne Mette G and Vaegter, Christian B and Raška, Jan and Cesnáriková, Soňa and Sedmík, Jiří and Trieu, Calvin and Weiss, Marjan M and Rosalina, Van Spaendonk and Vermunt, Lisa and Ozhegov, Georgii and Tesi, Niccolo and Hulsman, Marc and Januliene, Dovile and Moller, Arne and Bohačiaková, Dáša and Van Der Flier Wiesje, M. and Andersen, Olav M and Teunissen, Charlotte E and Holstege, Henne},
   article_location = {Hoboken},
   article_number = {2},
   doi = {https://doi.org/10.1002/alz.71042},
   keywords = {Alzheimer's Disease; cerebrospinal fluid (CSF); missense variants; quantitative immunoassay; soluble SORL1 (sSORL1); SORL1},
   language = {eng},
   issn = {1552-5260},
   journal = {ALZHEIMERS & DEMENTIA},
   title = {Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants},
   url = {https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71042},
   volume = {22},
   year = {2026}
}

TY  - JOUR
ID  - 2565351
AU  - De Waal Matthijs W, J. - Van Der Lee Sven, J. - Lunding, Melanie - Boonkamp, Lynn - Barrett, Nolan - Monti, Giulia - Jensen, Anne Mette G - Vaegter, Christian B - Raška, Jan - Cesnáriková, Soňa - Sedmík, Jiří - Trieu, Calvin - Weiss, Marjan M - Rosalina, Van Spaendonk - Vermunt, Lisa - Ozhegov, Georgii - Tesi, Niccolo - Hulsman, Marc - Januliene, Dovile - Moller, Arne - Bohačiaková, Dáša - Van Der Flier Wiesje, M. - Andersen, Olav M - Teunissen, Charlotte E - Holstege, Henne
PY  - 2026
TI  - Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants
JF  - ALZHEIMERS & DEMENTIA
VL  - 22
IS  - 2
SP  - 1-14
EP  - 1-14
PB  - WILEY
SN  - 15525260
KW  - Alzheimer's Disease
KW  - cerebrospinal fluid (CSF)
KW  - missense variants
KW  - quantitative immunoassay
KW  - soluble SORL1 (sSORL1)
KW  - SORL1
UR  - https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71042
N2  - INTRODUCTION: The sortilin-related receptor (SORL1) directs APP and A beta trafficking within the retromer pathway. Cleavage at the cell surface releases soluble SORL1 (sSORL1) into cerebrospinal fluid (CSF). We examined whether CSF-sSORL1 can serve as an in vivo marker of genetically impaired SORL1. METHODS: CSF-sSORL1 was quantified by enzyme-linked immunosorbent assay (ELISA) in 218 participants: 90 carriers of SORL1 variants, 78 SORL1-wildtype (WT) AD patients, and 50 SORL1-WT controls. RESULTS: sSORL1 concentrations were significantly lower in carriers of protein-truncating and damaging missense variants. In SORL1-WT patients, CSF-sSORL1 correlated with pTau181 but not with A beta 42 among AD patients, and did not differ between patients and controls. DISCUSSION: These findings suggest that impaired SORL1 trafficking reduces receptor delivery to the cell surface and thereby decreases sSORL1 shedding, supporting its potential use as a pathway-specific biomarker.
ER  -

DE WAAL MATTHIJS W, J.; J. VAN DER LEE SVEN; Melanie LUNDING; Lynn BOONKAMP; Nolan BARRETT; Giulia MONTI; Anne Mette G JENSEN; Christian B VAEGTER; Jan RAŠKA; Soňa CESNÁRIKOVÁ; Jiří SEDMÍK; Calvin TRIEU; Marjan M WEISS; Van Spaendonk ROSALINA; Lisa VERMUNT; Georgii OZHEGOV; Niccolo TESI; Marc HULSMAN; Dovile JANULIENE; Arne MOLLER; Dáša BOHAČIAKOVÁ; M. VAN DER FLIER WIESJE; Olav M ANDERSEN; Charlotte E TEUNISSEN a Henne HOLSTEGE. Soluble SORL1 in cerebrospinal fluid as a marker for functional impact of rare SORL1 variants. \textit{ALZHEIMERS \&{} DEMENTIA}. Hoboken: WILEY, 2026, roč.~22, č.~2, s.~1-14. ISSN~1552-5260. Dostupné z: https://doi.org/10.1002/alz.71042.

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