Degenerative changes in epinephrine tonic vasomotor neurons in Alzheimer's disease

Abstract

The C-1 region in the rostral ventral lateral medulla contains mainly epinephrine (Epi) neurons. These neurons are the tonic vasomotor center of the brain. We previously demonstrated changes in the enzymatic activity of phenylethanolamine N-methyltransferase (PNMT) in axon terminals and cell bodies of Epi neurons from the medulla of Alzheimer's disease (AD) brains. In this study, we investigated the perikarya of C-1 neurons for the morphometric, immunohistochemical and histochemical changes that are seen in severely affected regions of Alzheimer brain. The mean areas and size distributionsof C-1 neurons from 6 AD and 6 neurologically normal patients were compared using the Wilcoxon rank sum test and Kolmogorov-Smirnov z tests respectively. Additional brain sections from the C-1 region of AD and control individuals were stained with cresyl violet or immunostained with antibodies to the lysosomal hydrolase cathepsin D, Tau-2, Alz-50 and β-amyloid protein. The average area of C-1 neurons in AD brains was decreased 18.3%( P < 0.001) compared to the areas of the same cell population in age-matched control brains. A shift toward smaller sized C-1 neurons was seen in the AD cases. Nissl stain demonstrated a central chromatolytic appearance in 3.7% of AD neurons sampled. No β-amyloid deposits were detected histologically or immunocytochemically in the C-1 region of AD brains. Both Tau-2 and Alz-50 immunoreactivity was observed in occasional (1%) C-1 neurons from AD brains but not in controls. A small proportion (30%) of the C-1 neurons showing atrophy displayed increased cathepsin D immunoreactivity. Accumulation of hydrolase-laden lysosomes was marked only in atrophic neurons in contrast to at-risk neurons of the prefrontal cortex and hippocampus where lysosomal alterations precede degenerative changes. Mechanisms underlying degeneration of these neurons are discussed.