A new study recently published in the journal Annals of Neurology discussed the identification of what could be the earliest-known biomarker that is associated with the risk of developing Alzheimer’s disease. Results of the study showed that the biomarker was present within Cerebral Spinal Fluid (CSF) for at least a decade before any signs of dementia appear.
Dr. Ramon Trullas, leader of the study and research professor at the CSIC Institute of Biomedical Research of Barcelona and his team of researchers were able to demonstrate that a decrease in the overall content of mitochondrial DNA (or mtDNA) within CSF might indicate Alzheimer’s disease. The study’s hypothesis was that decreased mtDNA levels in CSF reflect the mitochondria’s diminished ability to power the brain’s neurons, leading to their deaths. As mtDNA concentration decreases, well-known Alzheimer’s biomarkers begin to appear (AB1-42, t-tau, and p-tau proteins), leading Dr. Trullas to suggest that the mtDNA depletion may be the earliest possible sign and predictor of the disease. Also, the use of mtDNA detection is unhampered during experiments that have difficulties with protein detection; with mtDNA having the ability to be readily quantified by real-time quantitative PCR (qPCR) or droplet digital PCR (ddPCR) within laboratory settings.
During the study, Dr. Trullas and his team were able to detect and reproducibly quantitate mtDNA using qPCR, which was carefully optimized by adhering to the MIQE guidelines. In order to validate their qPCR findings, Dr. Trullas’ team used Bio-Rad Laboratories’’ QX 100TM Droplet Digital TM PCR system. The digital system provided an absolute quantification of the targeted DNA molecules without needing a standard curve. Additionally, for their CSF analysis, the Droplet Digital PCR system did not require sample purification to remove any PCR inhibitors, as qPCR processes require.
1) Petar Podlesniy, Joana Figueiro-Silva, Albert Llado, Anna Antonell, Raquel Sanchez-Valle, Daniel Alcolea, Alberto Lleo, Jose Luis Molinuevo, Nuria Serra, Ramon Trullas. Low CSF concentration of mitochondrial DNA in preclinical Alzheimer’s disease. Annals of Neurology, 2013; DOI: 10.1002/ana.23955
2) Chempetitive Group (2013, August 14). New biomarker could reveal Alzheimer’s disease years before onset. ScienceDaily. Retrieved August 19, 2013, from http://www.sciencedaily.com /releases/2013/08/130814101431.htm
By Lauren Horne, Intern, Roskamp Institute