Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients

Abstract

Quantitative cytochemistry of cytochrome oxidase (C.O.) was implemented in human brains to measure C.O. activity in the 3 main divisions of the inferior colliculus (IC): central (ICC), dorsal (ICD), and external (ICE). Units of C.O. activity (μmol/min/g tissue wet weight) were quantified in cellular compartments (overall average, neuropil, perikaryon, and dendrites) at the light microscope level using microdensitometry calibrated with C.O. activity standards measured spectrophotometrically. In a non-AD (Alzheimer's disease) control group (mean age = 79.6 ± 3.1 years, postmortem time = 6.9 ± 1.6 h), the ICC and ICD demonstrated higher ( p < 0.008) overall average activities (mean = 183.40 ± 18.7 and 184.98 ± 45.1 units, respectively) relative to the ICE (56.46 ± 15.9 units). Comparison of cellular morphometry (soma and nucleus area, perimeter, and diameter) revealed that the ICC contained cells of significantly larger soma size than in both the ICD and ICE ( p < 0.002). The distribution of soma diameters in the ICC of controls showed a clear bimodality, enabling the typing of the cells into larger and smaller than average soma diameter. Brains from patients with Alzheimer's disease (AD: mean age = 78.3 ± 2.9 years, postmortem time = 6.5 ± 1.3 h) were compared with the non-AD controls. Significant group differences were found only in the large cells of the ICC. The AD large cells showed a decrement in C.O. activity relative to the corresponding controls in overall average activity ( p < 0.032) and in peak activity of neuropil near the soma ( p < 0.012). These findings provide the first quantitative cytochemical data of C.O. activity in humans. They also suggest that cellular alterations in C.O. metabolism in AD affect predominantly specific groups of larger projection neurons while neighboring neurons are spared.