Cerebrospinal fluids from Alzheimer's disease patients exhibit neurotoxic effects on neuronal cell cultures

The European Journal of Neuroscience
Silvija JankeviciuteVilmante Borutaite

Abstract

A growing number of studies suggest amyloid-β and tau present in cerebrospinal fluid (CSF) and blood as putative biomarkers for Alzheimer's disease (AD). However, there is a question whether these compounds present in patients' bodily fluids can directly cause neurotoxic effects. We investigated effects of AD and other dementia (OD) patients' blood serum and CSF on viability of cells in primary cerebellar granule cell cultures. Overall, 59 individuals participated in the study from whom 55 samples of biological fluids were taken. Participants were classified into early (E-AD) and middle (M-AD) stages of AD, cognitively healthy control (HC) and OD groups. We found that concentrations of total and phosphorylated tau were higher in CSF from AD patients, while amyloid-β42 and amyloid-β40 in the serum was lower compared to HC. The most cytotoxic effects were induced by CSFs from M-AD patients which caused neuronal necrosis and suppressed microglial proliferation, whereas CSFs from the groups of other patients did not kill neurons. Serum and CSF from the E-AD group caused a reduction of neuronal numbers in cultures. There were no significant differences in levels of CSF biomarkers between the AD groups although both tau species in CS...Continue Reading

References

Aug 25, 2001·Annual Review of Neuroscience·V M LeeJ Q Trojanowski
Jun 12, 2002·The Journal of Biological Chemistry·Karie N DahlgrenMary Jo LaDu
Aug 18, 2006·FEBS Letters·Alberto Gómez-RamosJesús Avila
Feb 9, 2007·Journal of Neurochemistry·Dominic M Walsh, Dennis J Selkoe
Sep 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nicole SchupfRichard Mayeux
Jan 20, 2010·Lancet Neurology·Clifford R JackJohn Q Trojanowski
Feb 16, 2010·Archives of Biochemistry and Biophysics·Paulius CizasVilmante Borutaite
Feb 17, 2010·Nature Reviews. Neurology·Kaj BlennowHenrik Zetterberg
Feb 17, 2010·Cerebrospinal Fluid Research·Jan G Veening, Henk P Barendregt
Nov 5, 2010·Biochemistry·Cristian A Lasagna-ReevesRakez Kayed
Mar 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ming JinDennis J Selkoe
Feb 16, 2013·EMBO Reports·Amy M PoolerDiane P Hanger
Oct 23, 2013·Neurología : publicación oficial de la Sociedad Española de Neurología·U Gomez-PinedoA G García
Dec 24, 2013·Neuron·Clifford R Jack, David M Holtzman
Dec 25, 2013·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Heather M SnyderHoward M Fillit
Feb 8, 2014·Nature Medicine·Jing L Guo, Virginia M Y Lee
Dec 17, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Philip S InselUNKNOWN Alzheimer's Disease Neuroimaging Initiative
Jul 3, 2015·Brain : a Journal of Neurology·Tobias SkillbäckHenrik Zetterberg
Apr 5, 2016·Annals of Clinical and Translational Neurology·Shorena JanelidzeOskar Hansson
May 24, 2016·EBioMedicine·Urmi SenguptaRakez Kayed
Jun 1, 2016·Scientific Reports·Shorena JanelidzeOskar Hansson
Nov 1, 2016·Journal of Neurochemistry·Eric Karran, Bart De Strooper
Oct 16, 2016·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Scott E CountsElliott J Mufson
Oct 16, 2016·Acta Neuropathologica·Elisabeth Sanchez-MejiasJavier Vitorica
Feb 1, 2017·Molecular Brain·Daisuke TanokashiraWataru Araki
Feb 20, 2018·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Olivier HanonUNKNOWN BALTAZAR study group
Feb 24, 2018·The EMBO Journal·Susanne WegmannBradley T Hyman

❮ Previous
Next ❯

Citations

Oct 2, 2020·Molecular Neurobiology·Katryna PampuscenkoVilmante Borutaite
Mar 14, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Alida SpalloniPatrizia Longone

❮ Previous
Next ❯

Related Concepts

Related Feeds

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.