A IDIBAPS-IIBB-CSIC team proposes a potential biomarker for early diagnosis of Alzheimer's disease

The search for a reliable way to diagnose Alzheimer's disease is one of the great challenges of modern biomedicine. IDIBAPS-IIBB-CSIC Neurobiology Unit, led by Dr. Ramon Trullás, has discovered a potential biomarker that, if confirmed, could change the fundamentals of the disease. According to the study published in Annals of Neurology, with Petar Podlesniy and Joana Figueiro-Silva as its first authors, patients in preclinical stages of the disease may present reduced levels of mitochondrial DNA in the cerebrospinal fluid. The study involved other basic researchers from IDIBAPS-IIBB-CSIC, like Dr. Nuria Serra, and clinical researchers as Dr. Albert Lladó, Dr. Anna Antonell, Dr. Raquel Sánchez-Valle and Dr. Jose Luis Molinuevo from IDIBAPS - Hospital Clínic, with the support of the CIBER on Neurodegenerative Diseases (CIBERNED).

The complexity of Alzheimer's disease, as well as its interaction with other dementias and normal aging process, makes an accurate diagnosis difficult. Despite the great efforts invested in better understanding this disease, a 100% reliable diagnosis is only possible when analyzing the brain after the patient’s death. It would be an important advance to design tools for effectively diagnosing it before clinical symptoms appear. This would also facilitate the design of clinical studies to verify the response to different treatments of patients in the early stages of evolution.

In the present study investigators analyzed the cerebrospinal fluid of patients with biochemical indicators related to the disease but who still had no clinical symptoms. These indicators, such as decreased beta-amyloid or increased tau in the cerebrospinal fluid, require complex quantitative techniques and it is still unknown whether they are a cause or a consequence of the disease. In pre-clinical patient samples cerebrospinal fluid contained low levels of mitochondrial DNA, the genetic material of mitochondria, which are as the energetic motor of cells. No other cell organelle, apart from the core, contains DNA. This observation was replicated in another cohort of pre-clinical patients, courtesy of Hospital de Sant Pau, and, finally, with a third group of young patients with a mutation that causes Alzheimer's at an early age. All of them had reduced levels of mitochondrial DNA in the cerebrospinal fluid.

In case the effectiveness of this finding is confirmed in future studies, it would be a new biomarker for Alzheimer's disease very easy to detect through widespread and simple techniques such as Polymerase Chain Reaction (PCR). In addition, the study published in Annals of Neurology (1), which has received a positive editorial commentary in Nature Reviews Neurology (2), suggests the possibility that the regulation of the number of copies of mitochondrial DNA could be important in the origins of this dementia. IIBB-CSIC-IDIBAPS researchers confirmed, through microscopic techniques, that mitochondria from patients in the early stages of the disease show an altered behaviour, reducing their fission and fusion activity. It is necessary to further investigate and replicate these results in other laboratories to properly assess the impact of this discovery.

References: (1) Podlesniy P, Figueiro-Silva J, Llado A, Antonell A, Sanchez-Valle R, Alcolea D, Lleo A, Molinuevo JL, Serra N, Trullas R. Low CSF concentration of mitochondrial DNA in preclinical Alzheimer's disease. Ann Neurol. 2013 Jun 22. doi: 10.1002/ana.23955. [Epub ahead of print] Read the Abstract (2) Kingwell K. Alzheimer disease: CSF levels of mitochondrial DNA-a new biomarker for preclinical Alzheimer disease? Nat Rev Neurol. 2013 Jul 9. doi: 10.1038/nrneurol.2013.134. [Epub ahead of print] Read the Abstract

More information at CIBERNED.