Brain Oligomeric β-Amyloid but Not Total Amyloid Plaque Burden Correlates With Neuronal Loss and Astrocyte Inflammatory Response in Amyloid Precursor Protein/Tau Transgenic Mice

• DOI: 10.1097/nen.0b013e318217a118
• Publication Date: 2011-04-12T06:40:40Z
• Authors: Bibiana DaRocha-S...; Thomas C. Scotton; Mireia Coma; Alberto Serrano-Pozo; Tadafumi Hashimoto; Lidia Serenó; Marta Rodríguez; Belen Sánchez; Bradley T. Hyman; Teresa Gómez-Isla
• Keywords: Entorhinal cortex; Amyloid (mycology); P3 peptide

It has long been assumed that β-amyloid (Aβ) had to assemble into fibrillar amyloid plaques exert its neurotoxic effects in Alzheimer disease. An alternative hypothesis is soluble oligomers ofAβ play a much larger role neuronal damage than the insoluble component. We have tested these competing hypotheses vivo by studying clinicopathologic correlates of oligomeric Aβ species and classic brains double-transgenic APP-tau mice up 17 months age. Biochemical immunohistochemical measures brain exponentially increased with Oligomeric load correlated morphological markers deposition. In contrast total plaque burden, amount deposits labeled conformational epitope-specific antibody Nab61 closely loss numbers astrocytes entorhinal cortex CA1 hippocampal subfield. However, like other measurements, burden did not correlate well memory deficits mice. The number glial fibrillary acidic protein-positive most tightly impairment cell loss. Based on findings, we hypothesize astrocyte response, which likely triggered accumulation, adversely affects cognition might also contribute death this model.