Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid

Synaptic pathology has been identified in pre-clinical stages of Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, and Parkinson's disease, as well as certain psychiatric disorders.

“In fact, synaptic pathology has been identified in pre-clinical stages of AD, FTD, dementia with Lewy bodies, and Parkinson’s disease, as well as certain psychiatric disorders [5–7].”

Synaptic dysfunction and loss of synaptic plasticity are fundamental processes that underlie several neurodegenerative disorders from early stages.

“Synaptic dysfunction and loss of synaptic plasticity are fundamental processes that underlie several neurodegenerative disorders from early stages.”

A recent proteomic analysis of CSF revealed a panel of synaptic biomarkers that were expressed differentially through the progression of Alzheimer's disease stages, including glutamate ionotropic receptor-4 and vesicle-associated membrane protein-2.

“A recent proteomic analysis of CSF revealed a panel of synaptic biomarkers that were expressed differentially through the progression of AD disease stages.”

GluR4 was recently identified as a biomarker that demonstrates preclinical changes in AD patients before neurodegeneration and Tau pathology, although its diagnostic and prognostic value remains to be evaluated in depth.

“GluR4 was recently identified as a biomarker that demonstrates preclinical changes in AD patients before neurodegeneration and Tau pathology, although the diagnostic and prognostic value of this AMPA receptor complex protein remains to be evaluated in depth [5, 7].”

The absence of correlation of GluR4 in disease states could be an indicator of lack of normal physiology and its possible use as a biomarker for disease prognosis at early stages.

“This absence of correlation of GluR4 in disease states could be an indicator of lack of normal physiology and its possible use as a biomarker for disease prognosis at early stages [5, 29].”

Synaptic dysfunction is an early pathological event in many neurodegenerative disorders and may precede neuronal loss.

“Synapse dysfunction is emerging as one of the earliest pathological events in many neurodegenerative disorders, and may precede neuronal loss (Gong and Lippa 2010; Janezic et al. 2013; Lleó et al. 2019; Lui et al. 2016; Marttinen et al. 2015; Masliah et al. 2001).”