Nerve growth factor (NGF) pathway biomarkers in Down syndrome prior to and after the onset of clinical Alzheimer's disease

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. We examined levels of NGF pathway proteins (proNGF, neuroserpi...

Descripción completa

Detalles Bibliográficos
Autores: Pentz, Rowan, Iulita, M. Florencia|||0000-0002-3360-4498, Ducatenzeiler, Adriana, Videla Toro, Laura|||0000-0002-9748-8465, Benejam, Bessy|||0000-0002-6789-8615, Carmona Iragui, Maria|||0000-0001-6914-2339, Blesa, Rafael|||0000-0003-4026-2884, Lleó, Alberto|||0000-0002-2568-5478, Fortea, Juan|||0000-0002-1340-638X, Cuello, AC.|||0000-0003-2143-2745
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:247512
Acceso en línea:https://ddd.uab.cat/record/247512
https://dx.doi.org/urn:doi:10.1002/alz.12229
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
Biomarkers
Blood
Cerebrospinal fluid
Cholinergic
Down syndrome
Metalloproteases
MMP-1
MMP-3
MMP-9
Nerve growth factor
Neuroserpin
NGF metabolic pathway
Plasma
ProNGF
Tissue plasminogen activator
Descripción
Sumario: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. 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). 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. 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.

Similares en LA Referencia