FREQUENCY-ANALYSIS OF CATECHOLAMINE AXONAL MORPHOLOGY IN HUMAN BRAIN .2. ALZHEIMERS-DISEASE AND HIPPOCAMPAL SYMPATHETIC INGROWTH

We have examined the various diverse morphologies of catecholamine axo ns in the brains of patients with Alzheimer's disease. Alzheimer's dis ease and aged control brain tissue were obtained by a rapid autopsy pr otocol (mean postmortem delay < 1 h). Tissue blocks from the superior frontal cortex (Brodmann area 9), the hippocampal gyrus, and the calca rine cortex (Brodmann area 17) were processed for identification of ca techolamine axons using tyrosine hydroxylase immunocytochemistry. A to tal of 1275 tyrosine hydroxylase immunoreactive axons were randomly sa mpled from coded sections and classified into one of six distinct axon -type categories. The axon classification from patients with Alzheimer 's disease significantly differed from those of an age-matched control population in the hippocampus. The Alzheimer's disease brains were de creased in the frequency of very long, thin, tyrosine hydroxylase immu noreactive axons (type 1) and had an increased frequency of shorter, t ortuous, axons (type 3). These selective quantitative shifts in hippoc ampal catecholaminergic axon morphology are consistent with the hypoth esis that sympathetic noradrenergic axons invade the hippocampus of pa tients with Alzheimer's disease. Multivariate modeling of the frequenc y sampling data found that the axon type classification scheme success fully predicted the presence of Alzheimer's disease. In particular, th e use of quantitative neuroanatomical measures of the catecholaminergi c system in human brain tissue was found to have errorless predictive ability with respect to late onset (> 75 years) Alzheimer's disease. I n summary, the use of quantitative neuroanatomical measures of catecho lamine axonal morphologies in Alzheimer's disease brain tissue identif ied a specific frequency shift which may represent hippocampal sympath etic ingrowth and this unique measure was found to have predictive uti lity with respect to Alzheimer's disease.