Rm. Booze et al., FREQUENCY-ANALYSIS OF CATECHOLAMINE AXONAL MORPHOLOGY IN HUMAN BRAIN .2. ALZHEIMERS-DISEASE AND HIPPOCAMPAL SYMPATHETIC INGROWTH, Journal of the neurological sciences, 119(1), 1993, pp. 110-118
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.