Fibrillar beta-amyloid (Aβ) (1-42) elevates extracellular Aβ in cultured hippocampal neurons of adult rats

Alzheimer's disease (AD) is a chronic disorder with progressive neurodegeneration associated with aging and is characterized by fibrillar beta-amyloid (A[) deposits in the brain. Although the increased production of A beta seems to play a noticeable role in AD pathogenesis and its progression, all the mechanisms which are involved in this extracellular A beta elevation are not known completely. In the present study, we used adult hippocampal neuronal culture as an in vitro model which is favorable for adult neurodegenerative diseases' studies. We introduced a toxic concentration for fibrillar A beta 1-42 in adult neurons which was much lower from the toxic concentration in embryonic neurons. To determine the effect of fibrillar A beta 1-42 which is the most toxic part of amyloid plaques, on extracellular A beta 1-40, as the main part of beta APP proteolysis products, we treated the neurons with fibrillar A beta 1-42 at nontoxic concentrations of 2 x 10(-6), 2 x 10(-5) and 2 x 10(-4) mu M and measured extracellular A beta 1-40. Our findings show that even very low levels of fibrillar A beta 1-42 can contribute to subsequent extracellular A elevation in a dose dependent manner. These results suggest that even low levels of fibrillar A may have deleterious actions if it remains in extracellular space for a period of time. (C) 2007 Elsevier B.V. All rights reserved.