An analysis of the morphology of senile plaques in Down's syndrome patients of different ages using immunocytochemical and lectin histochemical techniques.

The morphology of the senile plaque (SP), within the hippocampus and the temporal cortex, has been examined in 21 patients with Down's syndrome (DS), dying between the ages of 13 and 65 years, using immunocytochemical and lectin histochemical methods, as well as with a conventional silver staining technique. The earliest changes detectable within these areas of brain in the younger patients involved a fine diffuse deposition of amyloid (A4) protein and a uniform granular accumulation of an oligosaccharide recognized by the lectin from Canavalia ensiformis (ConA). At this stage, these 'pre-plaque' areas are unrecognizable using silver staining. Later the conventional SP morphology becomes apparent; the A4 protein aggregates into the usual plaque core and neurites appear with silver staining. The fine ConA positive material concentrates into large clumps and becomes recognizable by other lectins such as PSA, WGA and ePHA, which bind to mannose containing structures in an increasingly complex form. It is suggested that the development of the pathological changes of Alzheimer's disease, in patients with DS (and also in AD itself) involves a primary deposition of amyloid protein in conjunction with the accumulation of an as yet unidentified oligosaccharide. These changes precede the neuronal response that is characterized by the formation of neurites and the accumulation of neurofibrillary tangles that ultimately leads to cell death.