Parkinson's disease patients had significantly higher serum levels of AT1 and ACE2 autoantibodies compared to healthy controls, with AT1 autoantibody levels increasing the odds of PD by 7.4% per unit.
Case-Control (n=223)
Yes
Are AT1 and ACE2 autoantibodies elevated in Parkinson's disease and do they contribute to disease progression?
Dysregulation of renin-angiotensin system autoantibodies (AT1 and ACE2) may contribute to Parkinson's disease progression, providing a rationale for repurposing AT1 blockers (ARBs) as a neuroprotective treatment.
Odds Ratio: 1.07 (95% CI 1.03–1.13)
Absolute Event Rate: 8.923% vs 7.556%
p-value: p=0.0019
The role of autoimmunity in neurodegeneration has been increasingly suggested. The renin-angiotensin system (RAS) autoantibodies play a major role in several peripheral inflammatory processes. Dysregulation of brain RAS has been involved in neuroinflammation and neurodegeneration. We aimed to know whether angiotensin type-1 receptor (AT1) autoantibodies (AT1 agonists) and angiotensin-converting enzyme 2 (ACE2) autoantibodies (ACE2 antagonists) may be involved in Parkinson's disease (PD) progression and constitute a new therapeutical target. Both AT1 and ACE2 serum autoantibodies were higher in a group of 117 PD patients than in a group of 106 controls. Serum AT1 autoantibodies correlated with several cytokines, particularly Tumor Necrosis Factor Ligand Superfamily Member 14 (TNFSF14, LIGHT), and 27-hydroxycholesterol levels. Serum ACE2 autoantibodies correlated with AT1 autoantibodies. Both autoantibodies were found in cerebrospinal fluid (CSF) of four PD patients with CSF samples. Consistent with the observations in patients, experimental dopaminergic degeneration, induced by 6-hydroxydopamine, increased levels of autoantibodies in serum and CSF in rats, as well as LIGHT levels and transglutaminase activity in rat substantia nigra. In cultures, administration of AT1 autoantibodies enhanced dopaminergic neuron degeneration and increased levels of neuroinflammation markers, which was inhibited by the AT1 antagonist candesartan. The results suggest dysregulation of RAS autoantibodies as a new mechanism that can contribute to PD progression. Therapeutical strategies blocking the production, or the effects of these autoantibodies may be useful for PD treatment, and the results further support repurposing AT1 blockers (ARBs) as treatment against PD progression.
Labandeira et al. (Tue,) conducted a case-control in Parkinson's disease (n=223). Parkinson's disease vs. Healthy controls was evaluated on AT1-AA serum concentration (U/mL) (OR 1.07, 95% CI 1.03-1.13, p=0.0019). Parkinson's disease patients had significantly higher serum levels of AT1 and ACE2 autoantibodies compared to healthy controls, with AT1 autoantibody levels increasing the odds of PD by 7.4% per unit.