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Nerve growth factor (NGF) pathway biomarkers in Down syndrome prior to and after the onset of clinical Alzheimer's disease: A paired CSF and plasma study
Author(s) -
Pentz Rowan,
Iulita M. Florencia,
Ducatenzeiler Adriana,
Videla Laura,
Benejam Bessy,
CarmonaIragui María,
Blesa Rafael,
Lleó Alberto,
Fortea Juan,
Cuello A. Claudio
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12229
Subject(s) - nerve growth factor , cerebrospinal fluid , medicine , alzheimer's disease , endocrinology , neurotrophin , neurology , pathology , psychology , disease , receptor , neuroscience
Background The discovery that nerve growth factor (NGF) metabolism is altered in Down syndrome (DS) and Alzheimer's disease (AD) brains offered a framework for the identification of novel biomarkers signalling NGF deregulation in AD pathology. Methods We examined levels of NGF pathway proteins (proNGF, neuroserpin, tissue plasminogen activator [tPA], and metalloproteases [MMP]) in matched cerebrospinal fluid (CSF)/plasma samples from AD‐symptomatic (DSAD) and AD‐asymptomatic (aDS) individuals with DS, as well as controls (HC). Results ProNGF and MMP‐3 were elevated while tPA was decreased in plasma from individuals with DS. CSF from individuals with DS showed elevated proNGF, neuroserpin, MMP‐3, and MMP‐9. ProNGF and MMP‐9 in CSF differentiated DSAD from aDS (area under the curve = 0.86, 0.87). NGF pathway markers associated with CSF amyloid beta and tau and differed by sex. Discussion Brain NGF metabolism changes can be monitored in plasma and CSF, supporting relevance in AD pathology. These markers could assist staging, subtyping, or precision medicine for AD in DS.