Resumo

Objectives: Alzheimer's disease (AD) is characterized by progressive neuronal degeneration and accumulation of extracellular deposits of fibrillar b-amyloid peptide (Aâ). The soluble oligomers of Aâ are potent neurotoxins in the Central Nervous System that may participate in the pathogenesis of AD. The neuronal degeneration induced by Aâ peptide has been linked to excitotoxicity mediated by NMDA-glutamate receptors. D-serine is an endogenous co-agonist of the NMDA receptor. This initial study aims to develop a methodology to study the levels of Aâ oligomers in cerebrospinal fluid (CSF) of patients with different stages of AD. We have also investigated the correlation between the levels of Aâ oligomers and the D-serine levels in brain tissue. Methods: Postmortem samples of CSF (N = 31) and hippocampus (N = 43) are from the Brain Bank of the Brazilian Cerebral Aging of the USP. Cases were classified according to the Clinical Dementia Rating (CDR). The levels of Aâ oligomers in CSF were assessed by immunodetection of the binding of the Aâ oligomers antibody in samples pre-filtered in centricon of 100 KDa. With this method we observed specific marking of Aâ oligomers. The levels of D-serine in homogenate of cerebral cortex and CSF were measured by HPLC. Results: Individuals in the early stage of dementia, CDR 1 (p<0,05), showed an increase in the levels of Aâ oligomers when compared with individuals without dementia. In contrast, we found no difference in the levels of Aâ oligomers in individuals with advanced stages of AD (CDR 2 and 3) and those without dementia. The levels of D-serine seem to be similarly altered. We observed a significant increase in the levels of D-serine in samples of CSF and hippocampus when comparing individuals CDR 0.5 with those without dementia. In more advanced stages of AD the levels of D-serine also returned to levels similar to those of individuals without dementia. Conclusion: These results open the possibility of using the levels of Aâ oligomers in CSF as a marker of AD progression. Changes in levels of Aâ oligomers with the development of AD were accompanied by similar changes in D-serine levels, suggesting a relationship between these two molecules. Understanding the relationship between oligomers of Aâ and D-serine can lead to the development of new therapeutic strategies for AD.