Fibrillar beta-amyloid (Abeta) (1-42) elevates extracellular Abeta 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 (Abeta) deposits in the brain. Although the increased production of Abeta seems to play a noticeable role in AD pathogenesis and its progression, all the mechanisms which are involved in this extracellular Abeta 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 Abeta1-42 in adult neurons which was much lower from the toxic concentration in embryonic neurons. To determine the effect of fibrillar Abeta1-42 which is the most toxic part of amyloid plaques, on extracellular Abeta1-40, as the main part of betaAPP proteolysis products, we treated the neurons with fibrillar Abeta1-42 at nontoxic concentrations of 2 x 10(-6), 2 x 10(-5) and 2 x 10(-4) microM and measured extracellular Abeta1-40. Our findings show that even very low levels of fibrillar Abeta1-42 can contribute to subsequent extracellular Abeta elevation in a dose dependent manner. These results suggest that even low levels of fibrillar Abeta may have deleterious actions if it remains in extracellular space for a period of time.
Majd
Shohreh
S
Department of Physiology, Shiraz University of Medical Sciences, Zand Avenue, Shiraz, Iran. majdsh@sums.ac.ir
Rastegar
Karim
K
Zarifkar
Asadollah
A
Takhshid
Mohammad Ali
MA
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology*; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)