Biochemical analysis of Aβ in APP23 and APP48 mice. a: Total Aβ42 levels detected by ELISA in forebrain hemispheres of 2–3 and 15-18-month-old APP23 and APP48 mice. At 2–3 months APP23 mice exhibited low amounts of Aβ42 whereas APP48 mice displayed significantly more Aβ42 in the brain. At 15–18 months APP48 mice showed more Aβ than at 2–3 months of age but APP23 mice exhibited several times more Aβ in the forebrain. b: For demonstration of the types of Aβ aggregates in APP23 and APP48 mice brain homogenates of 9-11-month-old animals were analyzed by SDS-PAGE and western blotting after preparation of the soluble, dispersible, membrane-associated and insoluble (plaque-associated) fraction. Soluble Aβ as detected with antibodies raised against Aβ1-17 (6E10) was restricted to APP23 mice. Dispersible, membrane-associated, and insoluble (plaque-associated, formic acid soluble) Aβ aggregates were found in both transgenic mouse lines. The Aβ detected in the insoluble fraction of the forebrain homogenates of APP48 mice represents Aβ aggregates that require formic acid pretreatment before analysis similar to plaque-associated Aβ in APP23 mice. Since APP48 mice did not develop Aβ plaques this insoluble Aβ presumably represented intracellular fibrillar aggregates, such as dendritic threads. Wild type controls did not exhibit detectable amounts of Aβ in all four fractions. The original western blots are depicted in Additional file
3 (ELISA data from APP23 mice were previously published in a different context
). ***p < 0.001 Welch-test.