In a study of
thioflavin S-stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic,
cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with
Alzheimer's disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with
Alzheimer's disease exhibit either neurofibrillary tangles or
senile plaques, and only a few display both. However, when sections were immunostained with the
antibodies 10D5 and AT8 or ALZ50, both
beta-amyloid and hyperphosphorylated
epitopes of
tau protein were found to be present in various concentrations in all the affected nuclei. Our findings suggest that each brainstem nucleus has a distinct vulnerability to
Alzheimer's disease-related pathological changes. Given that each nucleus has idiosyncratic neuroanatomical connections and prevailing neurochemical characteristics, the heterogeneous collection of brainstem nuclei can be considered a suitable anatomical ground for further investigation of selective vulnerability in
Alzheimer's disease. The finding of severe pathological changes in some brainstem nuclei also raises the possibility that the dysfunction of these nuclei may contribute to the cognitive defects and increased rates of morbidity and mortality in patients with
Alzheimer's disease.