Own nodifferences in total APP holoprotein amounts between control bra…

Own nodifferences in total APP holoprotein amounts between control brain, brain from non-demented aged individuals and those with end-stage AD [54], by suggesting that there is an upregulation of APP when the first neurodegenerative changes occur in brain (Braak stage II-III), which possibly represents a compensatory CNS response to the first signs of damage in AD. It would also have been of interest to examine the abundance of APP C-terminal fragments in these tissues. Although we have previous experience in blotting APP fragments [73, 74], it was very difficult to detect these small protein fragments in these tissues presumably due to rapid postmortem degradation (data not shown). However, we measured total amounts of A1-40 and A1-42 in postmortem control and AD brain using specific Invitrogen ELISAs, as we have previously described [73, 74]. These analyses revealed that A1-40 amounts did not significant differ between any stage of AD andFig. 2 Transient elevations of total APP amounts in early AD, and persistent accumulation of A1-42 at end-stage disease. a Representative immunoblots of cortical homogenates from postmortem brain. Blots were probed with the 6E10 antibody to detect full-length amyloid precursor protein (APP) at 110 to 130 kDa. Blots were also probed with an anti-neuron-specific enolase (NSE, 45 kDa) as a loading control. b Bar graph shows APP amounts in brain following standardization to NSE protein in the same sample. A ELISAs were used to measure A1-40 and A1-42 amounts in pg mg-1 in these tissues. Bar graphs show (c) A1-40 and (d) A1-42 amounts in each sample. e postmortem brain sections immunostained with an anti-A antibody show the progressive development of amyloid plaque pathology in AD brain. CTRL: control (n = 5), Braak II AD (n = 4), Braak III AD (n = 3), Braak IV AD (n = 4), Braak V AD (n = 3), Braak VI AD (n = 5). Data is mean ?SEM. *p PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 increases in APP amounts are found transiently in Braak stage IIIII stage AD brain, a change that might reflect an, as yet unknown, compensatory response to early stages of damage in the nervous system. These changes in APP preceded the elevated A1-42 production and significant plaque deposition that was found in stage IV-VI AD brain.Calpain-1 activity is increased in Braak stage III brain and is sustained throughout disease progressionfound that levels of active CAST (holoprotein plus 37?75 kDa fragments) were significantly increased in Braak IV-V AD tissue (p Capecitabine control (Fig. 3c). There were also differences, some significant, in the amounts of inactive CAST relative to total CAST in all AD tissues (Fig. 3d), likely representing the increased total CAST apparent in AD brain that was detected by immunoblotting.Active caspase-3 amounts.