The present studies assessed the levels of [125I][Sar1,ILE8]angiotensin II-labelled
angiotensin AT1 and AT2 receptor recognition sites in homogenates of various brain
areas (including caudate nucleus, putamen, substantia nigra, hippocampus, frontal
cortex, temporal cortex and cerebellum) from patients with clinically diagnosed Parkinson's
disease, Huntington's disease and Alzheimer's disease and those from age-, sex- and
post-mortem delay-matched neurologically and psychiatrically normal patients. Radiolabelled
angiotensin AT1 receptor recognition site levels were significantly decreased by approximately
70%, 70% and 90% in the caudate nucleus, putamen and substantia nigra, respectively,
from patients with Parkinson's disease relative to matched controls. Furthermore,
radiolabelled angiotensin AT2 receptor levels were decreased by some 60% in the caudate
nucleus of patients with Parkinson's disease relative to control patients. In brain
tissue homogenates from patients with Huntington's disease, the angiotensin AT1 receptor
recognition site levels were decreased by approximately 30% in putamen relative to
the control patients whilst angiotensin AT2 receptor levels were increased by some
90% in the caudate nucleus relative to the control patients. In brain tissue homogenates
from patients with Alzheimer disease, the angiotensin AT2 receptor recognition site
levels were significantly increased by approximately 200% in the temporal cortex relative
to the control patients. The present results indicate that the reduction of angiotensin
AT1 and/or AT2 receptor recognition site levels in the caudate nucleus, putamen and
substantia nigra correlates with the principal neuropathology associated with Parkinson's
disease and as such indicates that at least a significant population of angiotensin
AT1 and AT2 receptors are located on the human dopaminergic nigrostriatal pathway.
In addition, the marked increase in the levels of angiotensin AT2 receptor recognition
sites in temporal cortex from patients with Alzheimer's disease correlates with some
other markers associated with the renin-angiotensin system previously investigated
in tissue from patients with this neurological disease.