Blood measure of neuronal death is exponentially higher with age, especially in females, and halted in Alzheimer's disease by GM-CSF treatment.

Stefan H Sillau, Christina Coughlan, Md Mahiuddin Ahmed, Kavita Nair, Paula Araya, Matthew D Galbraith, Alanna Ritchie, Athena Ching-Jung Wang, Mihret T Elos, Brianne M Bettcher, Joaquin M Espinosa, Heidi J Chial, Neill Epperson, Timothy D Boyd, Huntington Potter

Department of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.Department of Neurology and the University of Colorado Alzheimer's and Cognition Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. · pubmed

Paper

Abstract

Aging increases the risk of neurodegeneration, cognitive decline, and Alzheimer's disease (AD). We report that plasma concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and neurofilament light (NfL) become exponentially higher from ages 2 to 85 in cross-sectional samples, serving as neuronal death/damage biomarkers across the lifespan. UCH-L1 concentrations rise faster in females, who exhibit increased AD risk. Glial fibrillary acidic protein (GFAP) concentrations increase exponentially after age 40, especially in females. Age-adjusted UCH-L1, NfL, and GFAP plasma concentrations are greatly elevated in mildly cognitively impaired participants. Treatment of human AD trial participants with granulocyte-macrophage colony-stimulating factor (GM-CSF/sargramostim) apparently halts neuronal cell death: UCH-L1 biomarker concentrations are reduced to those of 5-year-old healthy controls. GM-CSF treatment also reduces neuronal apoptosis and astrogliosis in a rat model of AD. An exponential increase in neurodegeneration with age, accelerated by astrogliosis/inflammation, may underlie the contribution of aging to cognitive decline and AD and can be halted by GM-CSF/sargramostim treatment.

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Research summary

The paper claims that GM-CSF treatment can halt neuronal cell death in Alzheimer's disease by reducing specific biomarkers to levels seen in young healthy individuals. This research is relevant as it explores a potential intervention that addresses the underlying mechanisms of neurodegeneration associated with aging, rather than merely treating symptoms.

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