Beta-amyloid expression, release and extracellular deposition in aged rat brain slices.
Alzheimer's disease (AD) is characterized by beta-amyloid plaques, tau pathology, cholinergic cell death and inflammation. The aim of this study was to investigate whether beta-amyloid is generated, released and extracellularly deposited in organotypic brain slices. In developing slices, no amyloid-precursor protein (APP) was detectable; however, there was a strong upregulation in aging slices. In such slices, rat beta-amyloid(1-42) and -(1-40) peptides were found using four sequence-specific antibodies. APP and beta-amyloid were expressed in neurons and to a lesser extent in astrocytes. Beta-amyloid was secreted into the medium. Beta-amyloid was located extracellularly when aging slices were incubated with medium at pH 6.0 including apolipoprotein E4 (ApoE4). It is concluded that aging organotypic brain slices express beta-amyloid and that acidosis induces cell death with efflux of beta-amyloid and extracellular depositions, which is triggered by ApoE4. This novel in vitro model may enable us to investigate further the pathological cascade for AD and may be useful to explore future therapeutics.
Marksteiner
J
J
Laboratory of Psychiatry and Exp. Alzheimer's Research, Department of General Psychiatry, Innsbruck Medical University, Innsbruck, Austria.
Humpel
C
C
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4 / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D007211:Indoles; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C007293:DAPI; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase