Autoantibodies Toward the Angiotensin 2 Type 1 Receptor: A Novel Autoantibody in Alzheimer's Disease

J Alzheimers Dis. 2015;47(2):523-9. doi: 10.3233/JAD-150053.

Abstract

Background: Autoantibodies with agonist function are described in cardiovascular disorders. Since vascular risk factors are associated with an increased risk for Alzheimer's disease (AD), we investigated a potential association between antibodies to the angiotensin 2 type 1 receptor (anti-AT1R) and AD.

Objective: The primary objective of this study was to investigate the association between anti-AT1R and AD. The secondary objective was to investigate the association between clinical or biomarker features of AD and anti-AT1R.

Methods: Samples from patients with mild AD participating in a longitudinal study in Western Norway (n = 92, 65 [71%] females, mean age 74.8 [range 50-89]) and age- and gender-matched healthy controls (n = 102) were included. Cerebrospinal fluid (CSF) AD biomarkers were assessed in a subgroup of patients. Patients were examined annually, including Mini-Mental State Examination. ELISA was used to measure anti-AT1R in serum. Non-parametric tests were used for statistical calculations and a p < 0.05 was considered significant.

Results: AD patients had significantly higher levels of anti-AT1R compared with healthy controls (10.2 U/mL versus 8.1 U/mL, p = 0.04). This difference was found only in patients without hypertension and diabetes. Anti-AT1R levels correlated with CSF total tau (p = 0.03) and phosphorylated tau (p = 0.03) levels, and inversely with blood pressure in AD (Spearman R -0.277, p = 0.008).

Discussion: AD is associated with increased levels of anti-AT1R, and the antibodies correlated with CSF total, and phosphorylated tau levels. Further research is needed to understand the blood pressure response in AD without hypertension and a potential link between tau and anti-AT1R in AD.

Keywords: AT1R; autoimmunity; dementia; neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Norway / epidemiology
  • Receptor, Angiotensin, Type 2 / immunology*

Substances

  • Autoantibodies
  • Biomarkers
  • Receptor, Angiotensin, Type 2