Human Amyloid β42 High Sensitivity ELISA KIT

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.

Traumatic axonal injury (TAI) following traumatic brain injury (TBI) contributes to morbidity and mortality. TAI involves intra-axonal changes assumed to progress to impaired axonal transport (IAT), disconnection, and axonal bulb formation. Immunocytochemical studies employing antibodies to amyloid precursor protein (APP), a marker of IAT and RMO14, a marker of neurofilament compaction (NFC), have shown that TAI involves both NFC and IAT, with the suggestion that NFC leads to IAT. Recently, new data has suggested that NFC may occur independently of IAT. The objective of this study was to determine quantitatively the precise relationship between NFC and IAT. Following TBI, rats were studied at 30 min, 3 h, and 24 h. Using single-label immunocytochemistry employing the antibodies RMO14, APP, or a combined labeling strategy targeting APP/RMO14 in aggregate, the immunoreactive (IR) profiles were counted in the corticospinal tract (CSpT) and medial lemniscus (ML). In the CSpT, the number of axons demonstrating RMO14-IR approximated the number of axons showing APP-IR, with the APP-IR population showing a significant increase over 24 h (p < 0.05). The sum of both single-label counts equaled the aggregate APP/RMO14 numbers, demonstrating little relationship between NFC and IAT. In the ML, 75% of fibers demonstrated a separation of APP-IR and NFC-IR; however, 25% of the ML fibers showed co-localization of APP-IR and RMO14. The results of these studies indicate that, in the majority of damaged axons, NFC is not associated with IAT. Our findings argue for the use of multiple markers when evaluating the extent of TAI or the efficacy of therapies targeting the treatment of TAI.