Early Amyloid Deposition in the Medial Temporal Lobe of Young Down Syndrome Patients: A Regional Quantitative Analysis

The presence of the neuropathological alterations of Alzheimer's disease (AD) in essentially all older Down syndrome (DS) patients suggests that the examination of younger DS patients may clarify the early pathological progression of AD. We examined the hippocampus and parahippocampal-inferior temporal gyri of 42 DS patients (ages 4 days to 38 years) for the deposition of amyloid β protein (Aβ) using both a modified Bielschowsky stain and immunohistochemistry for Aβ protein. The parahippocampal and inferior temporal gyri demonstrated Aβ staining in cases as young as 8 years of age. As age and degree of Aβ deposition increased, staining included the CA-1/subiculum and dentate molecular layer followed then by the remainder of the CA hippocampal regions. The first neuritic plaques were observed in the CA-1/subiculum, despite this being a later region of Aβ deposition. Although Aβ staining increased with age, there was substantial variability in the severity of Aβ deposition within age groups. These results suggest that within the hippocampal/parahippocampal region there is a progressive stereotypic deposition of Aβ. The variable severity of Aβ deposition within age groups suggests that other factors, besides DS, may be contributing to the timing and severity of Aβ deposition.