Reference: Soc Neurosci Abst 2000; Vol. 26 (1), 497.


A.R. Koudinov1,2; N.V. Koudinova1,2*

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

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

Several lines of experimental evidence implicate cholesterol (Chl) in Alzheimer's (AD) disease. These studies and the immunodetection of amyloid beta (Ab, an important component of neuritic plaque, an AD hallmark), in brains of heart disease patients, illuminated another part of the AD puzzle, a link between AD and cardiovascular pathology on one hand, and between Chl and Ab on the other. However, there is no clear understanding of the joint role of these two molecules in the etiology of AD. In attempt to unravel this important issue we were looking for a lab animal, which would have modified both Chl and Ab metabolism. By altering rat brain Chl status with 2 % Chl diet we generated an animal model, expressing brain Ab very similar to vascular and plaque amyloid of pathologic aging and AD, as assessed by brain lipid synthesis studies (Soc Neurosci Abst 1999; 25(2): 1859) and extracellular immunohistochemistry with 4G8 monoclonal antibody in brain sections of Chl fed and control rats. We also studied tetanus induced long term potentiation (LTP), a marker of neuronal plasticity, by extracellular recording in CA1 of ex-vivo hippocampal slices. Chl fed rats showed partially reversible significant impairment of both induction and maintanance of LTP, represented as a normalized field excitatory postsynaptic potential (fEPSP) slope change versus time. Our results suggest that systemic and brain Chl turnover upregulation causes AD amyloid deposition and neuronal dysfunction.

Site Design and Programming © Alexei Koudinov, 2001.