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
Por:
Pentz, R, Iulita, MF, Ducatenzeiler, A, Videla, L, Benejam, B, Iragui, MC, Blesa, R, Lleo, A, Fortea, J, Cuello, AC
Publicada:
1 abr 2021
Resumen:
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.
Filiaciones:
Pentz, R:
McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada
Iulita, MF:
McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Ducatenzeiler, A:
McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada
Videla, L:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fdn Catalana Sindrome Down, Barcelona Down Med Ctr, Barcelona, Spain
Benejam, B:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fdn Catalana Sindrome Down, Barcelona Down Med Ctr, Barcelona, Spain
Iragui, MC:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fdn Catalana Sindrome Down, Barcelona Down Med Ctr, Barcelona, Spain
Blesa, R:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fdn Catalana Sindrome Down, Barcelona Down Med Ctr, Barcelona, Spain
Cuello, AC:
McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada
McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada
McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada
Univ Oxford, Dept Pharmacol, Oxford, England
Green Published, hybrid
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