Open AccessCSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM 2, neurodegeneration and cognitive decline
Author(s) -
SuárezCalvet Marc,
Capell Anja,
Araque Caballero Miguel Ángel,
MorenasRodríguez Estrella,
Fellerer Katrin,
Franzmeier Nicolai,
Kleinberger Gernot,
Eren Erden,
Deming Yuetiva,
Piccio Laura,
Karch Celeste M,
Cruchaga Carlos,
Paumier Katrina,
Bateman Randall J,
Fagan Anne M,
Morris John C,
Levin Johannes,
Danek Adrian,
Jucker Mathias,
Masters Colin L,
Rossor Martin N,
Ringman John M,
Shaw Leslie M,
Trojanowski John Q,
Weiner Michael,
Ewers Michael,
Haass Christian
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809712
Subject(s) - trem2 , microglia , neurodegeneration , biomarker , disease , cerebrospinal fluid , alzheimer's disease , cognitive decline , immunology , medicine , dementia , pathology , biology , inflammation , genetics
Progranulin ( PGRN ) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease ( AD ). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD . We measured PGRN in cerebrospinal fluid ( CSF ) in two of the best‐characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network ( DIAN ) and the Alzheimer's Disease Neuroimaging Initiative ( ADNI ). In carriers of AD causing dominant mutations, cross‐sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non‐carriers 10 years before the expected symptom onset. In late‐onset AD , higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM 2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD , it may together with sTREM 2 reflect microglial activation during the disease.