ALZHEIMER'S AMYLOID BETA: BIOLOGICAL WASTE OR ESSENTIAL PROTEIN?

N.V. Koudinova^1,2; T.T. Berezov ¹; A.A. Boldyrev^1*; A.R. Koudinov^1,2

1. Russian Acad Med Sci, Nat Mental Health Res Ctr, Inst Biomed Chem, Lab Clin Neurochem, Timoshenko 38-27, Moscow 121359, Russian Federation

2. Neurobiol and Biol Regulation, Weizmann Institute, Rehovot 76100, Israel

What Alois Alzheimer saw in early 1900s in brain samples from the first Alzheimer's (AD) case ever to be described in medical literature were senile plaques, composed mainly of amyloid beta protein (Ab, Science 1998;279:2037). Ab (first described by G. Glenner; BBRC 1984;120:885) is derived from amyloid b precursor protein (bPP) via still unknown proteolytic pathway. Its site of origin, biological function and role in AD are not clear and many scientists believe that Ab is just a biological waste. In 1992 several reports have shown that there is a soluble form of Ab which is normally produced by cells in culture and can be detected in plasma, CSF and brain tissue. This implied that the secretion of sAb is physiologic (until proved pathologic). Moreover, bPP processing (leading to its Ab-bearing C-terminus) is strongly conserved in animals from insecta to mammalia, suggesting that sAb can be involved in very basic and important metabolic pathways. Soluble Ab association with lipoproteins (first reported by us in 1994 and confirmed by others; FASEB J 1998;12:1097) suggests that sAb may have important function in lipid metabolism, shown to be altered in AD. In these terms an observation of the inhibition of cholesterol esterification in normal human plasma and neuronal cells, as well as tissue-, developmental- and neuronal activity status-dependent modulation of lipid synthesis by Ab peptides (Soc Neurosci Abst 1999;25:1859; Neurochem Res 2000;25:653) may reflect some of its functions, although the other role of sAb in vertebrates (like PKC modulation (J Neurochem 2001;76:758), antioxidant activity, etc.) can not be excluded.

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