The role of oxidative stress in the progression of Alzheimer's disease is shown to affect only the cellular level

Alzheimer's disease is the most common type of dementia and biomedical research is studying different areas to understand it in detail. Researchers at the University of Lleida (UdL) and the Institute of Biomedical Research of Lleida (IRBLleida) have led an investigation, in collaboration with the Pablo de Olavide University in Seville, which has shown that the role of oxidative stress in the progression of Alzheimer's disease affects only at the cellular level and instead, damage in extracellular fluids, such as plasma and cerebrospinal fluid, is ruled out. This lack of association may suggest that oxidative stress in Alzheimer's disease is probably well tolerated by proteins in these circulating fluids in the body.

"This research allows us to make progress in understanding the role of oxidative stress in the development and progression of Alzheimer's disease. The studies that have been done so far in this respect show inconsistent results due to the diversity in the methodology and small sample size, among others, and therefore the level of oxidative damage circulating at the systemic and central level in patients with Alzheimer's disease remains unclear" explained the first author of the article, Farida Dakterzada, from the Cognitive Disorders Unit of the University Hospital of Santa Maria de Lleida and researcher of the Cognition and Behaviour Study Group at IRBLleida.

Oxidative stress, the excess of oxygen that generates an uncontrolled presence of unstable molecules in the body that can attack the cell and cause disease, plays an important role in the development of Alzheimer's disease. Some studies have observed that this oxidative stress contributes to the loss of information processing capacity and the progression of Alzheimer's disease. The aim of this research was to determine whether this damage that occurs at the brain level could also be observed in different biological fluids. The findings demonstrate the need to study the brain directly in order to assess the impact of oxidative stress on Alzheimer's disease.

The research, which was recently published in the journal Redox Biology, was carried out on a sample of 289 people with Alzheimer's disease (103 people), mild cognitive impairment (92 people) and also people without these diseases (94 people) for comparative analysis. The research has attempted to decipher the association that may exist between the content of oxidative damage in plasma and cerebrospinal fluid and the diagnosis and progression of Alzheimer's disease using a very precise method, mass spectrometry. In addition, to find out the role of oxidative stress in the progression of Alzheimer's disease, patients have been followed for five years.

"Our results showed that there was no association between levels of oxidative damage in cerebrospinal fluid or plasma and the diagnosis of Alzheimer's disease or its progression," the researcher confirmed.

Alzheimer's disease is a progressive neurodegenerative disease characterised by an initial deterioration of memory that may ultimately affect other cognitive and behavioural abilities. The causes of its onset are unknown, but may include genetic, metabolic, lifestyle and environmental factors. A pre-dementia stage of the disease is mild cognitive impairment, in which people retain their functionality and independence in performing routine daily tasks.

The research has been carried out in collaboration with the Department of Experimental Medicine of the UdL and CIBERNED, Centre for Biomedical Research Network on Neurodegenerative Diseases. And the support of the Department of Health (PERIS 2019 SLT008/18/00050 and SLT002/16/00250), the Agency for Management of University and Research Grants (2021SGR 00761 and 2021SGR00990), the Ministry of Science, Innovation and Universities (grant RTI2018-099200-B-I00 and PID2022-143140OB-I00), the Ministry of Economic Affairs and Digital Transformation (PID2020-119978RB-I00), CIBERNED, the Alzheimer's Association (AARG-NTF-22-924702), the Junta de Andalucía (PY20_00858), the Andalucía-FEDER Programme (UPO-1380913), the Diputación de Lleida (PP10605 - PIRS2021) and the European Union ERDF fund ("A way to build Europe").

Image: The research team: Gerard Piñol, Mariona Jové, Reinald Pamplona and Farida Dakterzada

Article: Dakterzada F, Jové M, Cantero JL, Pamplona R, Piñoll-Ripoll G. Plasma and cerebrospinal fluid nonenzymatic protein damage is sustained in Alzheimer's disease. Redox Biol. 2023 Jun 4;64:102772. doi: 10.1016/j.redox.2023.102772. Epub ahead of print. PMID: 37339560.