ASTROCYTES IN ALZHEIMERS-DISEASE EXPRESS IMMUNOREACTIVITY TO THE VASOCONSTRICTOR ENDOTHELIN-1

The avidin-biotin peroxidase complex method and a polyclonal antiserum were used to investigate the distribution of endothelin-l-like immuno reactivity of cerebral astrocytes in autopsy cases of Alzheimer's dise ase compared with controls. The cases of Alzheimer's disease presented numerous astrocytes with intense endothelin-l-like immunoreactivity o f the cell body often extending into the finest ramifications of the c ell processes. Absorption of the antiserum by the corresponding antige n eliminated this immunostaining. The immunoreactive astrocytes were m ost consistently present in the subcortical white matter of the cerebr al hemispheres and the folia of the cerebellum. The immunoreactive cel ls were often located in small clusters close to blood vessels. Five o f the seven cases showed immunoreactive astrocytes in the molecular la yer of the cerebral cortex and three of the seven cases presented regi ons in which immunoreactive astrocytes appeared to be located in the p eriphery of plaques. The pens contained small groups of immunoreactive astrocytes in five of the cases. The cerebellum had such cells in six of the seven investigated patients. Immunoreactive astrocytes were ve ry rare in control cases without cerebral disease. Many nerve cells in the cerebral neocortex, hippocampus, cerebellum and pens of Alzheimer cases and controls exhibited endothelin-l-like immunoreactivity. Olig odendrocytes and endothelial cells of blood vessels of controls and Al zheimer cases did not show such immunoreactivity. The expression of en dothelin-l-like immunoreactivity in astrocytes of Alzheimer's disease probably reflects an increased content of endothelin-l. If endothelin- l is released from such astrocytes it may reach smooth muscle cells of the intracerebral blood vessels and disturb micro-circulation since t his compound is a most powerful vasoconstrictor peptide.