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 (Aβ) deposits in the brain. Although the increased production of Aβ seems to play a noticeable role in AD pathogenesis and its progression, all the mechanisms which are involved in this extracellular Aβ 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 Aβ1–42 in adult neurons which was much lower from the toxic concentration in embryonic neurons. To determine the effect of fibrillar Aβ1–42 which is the most toxic part of amyloid plaques, on extracellular Aβ1–40, as the main part of βAPP proteolysis products, we treated the neurons with fibrillar Aβ1–42 at nontoxic concentrations of 2 × 10− 6, 2 × 10− 5 and 2 × 10− 4 μM and measured extracellular Aβ1–40. Our findings show that even very low levels of fibrillar Aβ1–42 can contribute to subsequent extracellular Aβ elevation in a dose dependent manner. These results suggest that even low levels of fibrillar Aβ may have deleterious actions if it remains in extracellular space for a period of time.