Intraneuronal beta-amyloid immunoreactivity in the CNS.

The high degree of overlap in the neuropathologic outcome of Alzheimer's disease (AD), Down's Syndrome (DS), and coronary heart disease suggest a possible interrelationship. The pattern of hippocampal and cortical intraneuronal beta A4 immunoreactivity is strikingly similar in AD, DS, coronary heart disease, and two separate animal models of coronary heart disease. Cells in fascia dentata and large cortical neurons were beta A4 immunodecorated in half the AD and DS subjects studied. Similar neuronal staining occurred in half the age-matched coronary heart disease subjects, but was absent in each nonheart disease control investigated. Analogous accumulations of neuronal beta A4 immunoreactivity were induced in rabbit brain by dietary administration of high cholesterol, and this effect could be reversed by regression of the experimental diet. Decreased density (p < 0.05) and cellular staining intensity occurred after 2 weeks of control diet following 8 weeks of high cholesterol. Microgliosis accompanied the accumulation of beta A4 immunoreactivity in the cholesterol-fed rabbits and persisted after regression of the diet and decreases in neuronal beta A4 immunoreactivity. An identical pattern of neuronal beta A4 immunoreactivity was induced in the brains of adolescent pigs after acute ligation of the left anterior descending coronary artery (LAD) compared to surgical and anesthetic controls. The mean number of beta A4 immunoreactive neurons was significantly increased (p < 0.05) in the cortex and hippocampus of pigs with a ligated LAD compared to both control groups. Increased density and intensity of neuronal beta A4 immunoreactivity induced by ligation of the LAD was commensurate with the severity of the decreased cardiac output in the LAD group, but not in the anesthetic control groups with decreased cardiac output. The incidence of ALZ-50 (A68) immunoreactive neurons also increased in the ligated pigs compared to both control groups. The data suggest a neuronal origin of beta A4 immunoreactive peptide(s), which can be cleared from the brain by microglia after severe accumulation is induced. This could indicate that reduced clearance of beta-APP metabolic by-products could contribute to a metabolic backlog and redirection of peptide processing by microglia to extracellular deposition. Neuronal accumulation of beta A4 immunoreactivity could be due to the effect of circulating factors on brain function in both animals models. It is likely that animal models of coronary heart disease may be useful in disclosing the mechanism of SP formation and induction of ALZ-50 immunoreactivity irrespective of their pathoclinical significance.