Evidence of amyloid beta-protein immunoreactive early plaque lesions in Down's syndrome brains

An immunohistochemical study was carried out on the brains of 12 cases with Down's syndrome (ages 18 to 62) using a monoclonal antibody to amyloid beta-protein with formic acid pretreatment of the sections. Localized ill-defined, weakly immunostained areas with a reticulogranular appearance were the only neocortical lesions observed in two cases aged 31 years. The presence of similar immunoreactive areas with larger size were the predominant cerebral lesions seen in 3 cases who died at the ages of 37 or 38 years. These resembled the "type 3" immunoreactive lesions (lacking any obvious amyloid deposits or abnormal neurites) that were observed previously by us in Alzheimer's disease. In addition to these lesions, older cases of Down's syndrome over 50 years of age showed discrete senile plaques with substantial deposits of amyloid (the number of these lesions increased with age), and many neurofibrillary tangles and cerebrovascular amyloid deposits were also found in these cases. The present observations support the theory that the type 3 lesions are an early stage in senile plaque formation, and suggest that an extensive appearance of type 3 lesions easily detected by immunostaining with formic acid pretreatment is an early neuropathologic change in Alzheimer's disease.