Anti-APP monoclonal antibody, clone 363R7

Aims: We investigated the axonal morphological changes and expression of both tau protein and beta-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Methods: Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and beta-APP proteins in the medulla oblongata were examined. Results: (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of beta-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05). Conclusion: (a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of beta-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.

Pathogenic amyloid-beta peptide precursor (APP) mutations clustered around position 693 of APP-position 22 of the A beta sequence-are commonly associated with congophilic amyloid angiopathy (CAA) and intracerebral hemorrhages. In contrast, the Osaka (E693 Delta) intra-A beta APP mutation shows a recessive pattern of inheritance that leads to AD- like dementia despite low brain amyloid on in vivo positron emission tomography imaging. Here, we investigated the effects of the Osaka APP mutation on A beta accumulation and deposition in vivo using a newly generated APP transgenic mouse model (E22 Delta A beta) expressing the Osaka mutation together with the Swedish (K670N/M671L) double mutation. E22 Delta A beta mice exhibited reduced alpha-processing of APP and early accumulation of intraneuronal fibrillar A beta oligomers associated with cognitive deficits. In line with our in vitro findings that recombinant E22 Delta-mutated A beta peptides form amyloid fibrils, aged E22 Delta A beta mice showed extracellular CAA deposits in leptomeningeal cerebellar and cortical vessels. In vitro results from thioflavin T aggregation assays with recombinant A beta peptides revealed a yet unknown antiamyloidogenic property of the E693 Delta mutation in the heterozygous state and an inhibitory effect of E22 Delta A beta 42 on E22 Delta A beta 40 fibrillogenesis. Moreover, E22 Delta A beta 42 showed a unique aggregation kinetics lacking exponential fibril growth and poor seeding effects on wild-type A beta aggregation. These results provide a possible explanation for the recessive trait of inheritance of the Osaka APP mutation and the apparent lack of amyloid deposition in E693 Delta mutation carriers.