Characteristic developmental expression of amyloid β40, 42 and 43 in patients with Down syndrome

We immunohistochemically studied the expression of β-amyloid precursor protein (APP), Aβ40, Aβ42, and Aβ43 in the frontal lobes of 20 Down syndrome (DS) patients and 13 controls. The immunoreactivity for each antibody was different in the degree of intensity and the chronological pattern of expression. APP and Aβ43 immunoreactivity was increased in neurons initially, and then Aβ43 and 42 immunoreactivity appeared in diffuse plaques from 32 years of age. APP and Aβ43 were characteristically observed in axons around senile plaques. Finally, Aβ40 immunoreactivity was detected in the cores of senile plaques. This time course of immunoreactive expression may be related to the pathogenetic process of Alzheimer-type dementia in DS, and the axonal damage in senile plaques may lead to the formation of neurofibrillary tangles (NFT) or neuronal death through axonal flow disturbance and accumulation of Aβ43 in cortical neurons.