Neuronal loss and β-amyloid removal in the amygdala of people with Down syndrome☆

The decrease in the number of neurons free of neurofibrillary changes, neurons with neurofibrillary degeneration, and the total volume of beta-amyloid (A beta) deposits in the amygdala of people with Down syndrome and in late stages of Alzheimer disease were estimated by using morphometry and regression analysis. This model predicts that the duration of neurofibrillary changes from the pretangle stage to ghost tangles is approximately 4.7 years. The correlation between the decrease in the number of neurons and the decrease in the amount of A beta indicates that amyloid deposition is associated with neurons and that loss of neurons causes decrease in A beta deposition. The presence of neurons only with neurofibrillary tangles, and the absence of the amyloid deposits predicted by regression analysis suggest that neurons with tangles are not engaged in amyloid deposition. The disappearance of amyloid by approximately 2.2 years after loss of neurons free of neurofibrillary changes indicates that A beta deposits are degradable and removable and that even in severely atrophic amygdala, there are mechanisms of amyloid resolution. This study shows that in normal aging in the amygdala, extracellular A beta appears later than neurofibrillary changes.