Down patients: Extracellular preamyloid deposits precede neuritic degeneration and senile plaques

Using anti-SP28 (a polyclonal antibody to a 28 residue synthetic peptide homologous to the NH₂-terminal region of the Alzheimer amyloid β-protein) to investigate the cerebral cortex of 6 Down patients aged 6-55 y, we found that, besides senile plaques and congophilic vessels, extracellular deposits unrelated to degenerating neurites, tangle-bearing neurons or congophilic vessels were labelled. These deposits were similar to the extracellular deposits previously observed in the cerebral cortex of Alzheimer patients and non-demented individuals. The material accumulated in the deposits did not react with Congo red, thioflavine S or, on some occasions, silver salts and therefore might have been constituted by β-protein precursors lacking the molecular conformation of amyloid fibrils. Age-related analysis of the cortical lesions in Down patients suggested that such extracellular deposits precede degenerating neurites and evolve into senile plaques.