Acetylcholinesterase fibers and the development of senile plaques

A new, highly sensitive histochemical technique for actylcholinesterase (AChE) was applied to a study of Alzheimer's disease brain tissue. Many immature senile plaques were seen to be developing along AChE-positive axons in the hippocampus and neocortex. Single fibers often displayed multiple lesions, showing stages of initial swelling, ballooning with the appearance of AChE in the surrounding extra-axonal space, and development of an AChE-amyloid intense core accompanied by a weakly staining AChE-positive halo. Except for the core and halo, AChE-positive material was seldom detected in so-called mature plaques which are large and incorporate many degenerating neuritic elements surrounding an amyloid core. Lesion data in rats established the relationship between AChE-positive neocortical axons and medial basal forebrain cholinergic cells. In Alzheimer's disease tissue, many degenerating neurons in the basal forebrain were detected by the AChE histochemical stain, along with pathological alterations in the proximal axons en route to their cortical terminal fields. These data provide direct evidence of an association between the cholinergic system of the basal forebrain and the early formation of senile plaques in the cortex in Alzheimer's disease.