Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals

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Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals. / Molgaard, Simon; Demontis, Ditte; Nicholson, Alexandra M; Finch, Nicole A; Petersen, Ronald C; Petersen, Claus M; Rademakers, Rosa; Nykjaer, Anders; Glerup, Simon.

In: Experimental Gerontology, Vol. 84, 11.2016, p. 96-100.

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Molgaard, Simon ; Demontis, Ditte ; Nicholson, Alexandra M ; Finch, Nicole A ; Petersen, Ronald C ; Petersen, Claus M ; Rademakers, Rosa ; Nykjaer, Anders ; Glerup, Simon. / Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals. In: Experimental Gerontology. 2016 ; Vol. 84. pp. 96-100.

Bibtex

@article{e3827401396744a7ab3ad8e398a61a9a,
title = "Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals",
abstract = "Mutations in progranulin are a major cause of frontotemporal lobe degeneration (FTLD). Hence, plasma progranulin is an attractive biomarker in FTLD but poorly reflects levels in cerebrospinal fluid (CSF), suggesting tissue-specific regulation of progranulin levels. Sortilin was recently identified as a progranulin scavenger receptor that destines it for lysosomal degradation. Proteolysis or alternative splicing generates soluble sortilin variants that retain progranulin binding and potentially functions as a decoy receptor. In the present study, we analyzed soluble sortilin and progranulin in plasma and CSF in 341 aging individuals. We found that soluble sortilin exists in CSF in ten-fold molar excess compared to progranulin and observed a highly significant positive correlation between soluble sortilin and progranulin levels in CSF but not in plasma. However, carriers of the minor allele of SNP rs646776 in SORT1 encoding sortilin displayed significantly increased soluble sortilin and reduced progranulin specifically in plasma but not in CSF. Taken together, our findings suggest that soluble sortilin may affect progranulin levels in both a tissue-specific and genotype-dependent manner.",
author = "Simon Molgaard and Ditte Demontis and Nicholson, {Alexandra M} and Finch, {Nicole A} and Petersen, {Ronald C} and Petersen, {Claus M} and Rosa Rademakers and Anders Nykjaer and Simon Glerup",
note = "Copyright {\circledC} 2016. Published by Elsevier Inc.",
year = "2016",
month = "11",
doi = "10.1016/j.exger.2016.09.002",
language = "English",
volume = "84",
pages = "96--100",
journal = "Experimental Gerontology",
issn = "0531-5565",
publisher = "Elsevier Inc",

}

RIS

TY - JOUR

T1 - Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals

AU - Molgaard, Simon

AU - Demontis, Ditte

AU - Nicholson, Alexandra M

AU - Finch, Nicole A

AU - Petersen, Ronald C

AU - Petersen, Claus M

AU - Rademakers, Rosa

AU - Nykjaer, Anders

AU - Glerup, Simon

N1 - Copyright © 2016. Published by Elsevier Inc.

PY - 2016/11

Y1 - 2016/11

N2 - Mutations in progranulin are a major cause of frontotemporal lobe degeneration (FTLD). Hence, plasma progranulin is an attractive biomarker in FTLD but poorly reflects levels in cerebrospinal fluid (CSF), suggesting tissue-specific regulation of progranulin levels. Sortilin was recently identified as a progranulin scavenger receptor that destines it for lysosomal degradation. Proteolysis or alternative splicing generates soluble sortilin variants that retain progranulin binding and potentially functions as a decoy receptor. In the present study, we analyzed soluble sortilin and progranulin in plasma and CSF in 341 aging individuals. We found that soluble sortilin exists in CSF in ten-fold molar excess compared to progranulin and observed a highly significant positive correlation between soluble sortilin and progranulin levels in CSF but not in plasma. However, carriers of the minor allele of SNP rs646776 in SORT1 encoding sortilin displayed significantly increased soluble sortilin and reduced progranulin specifically in plasma but not in CSF. Taken together, our findings suggest that soluble sortilin may affect progranulin levels in both a tissue-specific and genotype-dependent manner.

AB - Mutations in progranulin are a major cause of frontotemporal lobe degeneration (FTLD). Hence, plasma progranulin is an attractive biomarker in FTLD but poorly reflects levels in cerebrospinal fluid (CSF), suggesting tissue-specific regulation of progranulin levels. Sortilin was recently identified as a progranulin scavenger receptor that destines it for lysosomal degradation. Proteolysis or alternative splicing generates soluble sortilin variants that retain progranulin binding and potentially functions as a decoy receptor. In the present study, we analyzed soluble sortilin and progranulin in plasma and CSF in 341 aging individuals. We found that soluble sortilin exists in CSF in ten-fold molar excess compared to progranulin and observed a highly significant positive correlation between soluble sortilin and progranulin levels in CSF but not in plasma. However, carriers of the minor allele of SNP rs646776 in SORT1 encoding sortilin displayed significantly increased soluble sortilin and reduced progranulin specifically in plasma but not in CSF. Taken together, our findings suggest that soluble sortilin may affect progranulin levels in both a tissue-specific and genotype-dependent manner.

U2 - 10.1016/j.exger.2016.09.002

DO - 10.1016/j.exger.2016.09.002

M3 - Journal article

C2 - 27612602

VL - 84

SP - 96

EP - 100

JO - Experimental Gerontology

JF - Experimental Gerontology

SN - 0531-5565

ER -