Upregulation Of Cortical A(2a) Adenosine Receptors Is Reflected In Platelets Of Patients With Alzheimer'S Disease

Background: Alzheimer's disease (AD) is a neurodegenerative pathology covering about 70% of all cases of dementia. Adenosine, a ubiquitous nucleoside, plays a key role in neurodegeneration, through interaction with four receptor subtypes. The A(2A) receptor is upregulated in peripheral blood cells of patients affected by Parkinson's and Huntington's diseases, reflecting the same alteration found in brain tissues. However, whether these changes are also present in AD pathology has not been determined.Objective: In this study we verified any significant difference between AD cases and controls in both brain and platelets and we evaluated whether peripheral A(2A) receptors may reflect the status of neuronal A(2A) receptors.Methods: We evaluated the expression of A(2A) receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, in postmortem AD patients and control subjects, through [H-3]ZM 241385 binding experiments. The same analysis was performed in peripheral platelets from AD patients versus controls.Results: The expression of A(2A) receptors in frontal white matter, frontal gray matter, and hippocampus/entorhinal cortex, revealed a density (Bmax) of 174 +/- 29, 219 +/- 33, and 358 +/- 84 fmol/mg of proteins, respectively, in postmortem AD patients in comparison to 104 +/- 16, 103 +/- 19, and 121 +/- 20 fmol/mg of proteins in controls (p < 0.01). The same trend was observed in peripheral platelets from AD patients versus controls (Bmax of 214 +/- 17 versus 95 +/- 4 fmol/mg of proteins, respectively, p < 0.01).Conclusion: AD subjects show significantly higher A(2A) receptor density than controls. Values on platelets seem to correlate with those in the brain supporting a role for A(2A) receptor as a possible marker of AD pathology and drug target for novel therapies able to modify the progression of dementia.