This is Great News for Alzheimers........
AZD-103/ELND005 doesn't just prevent the plaques seen in Alzheimers .....it Prevents Neuronal Cell Death as shown in this study. This Study should be required reading for all Longs.....Puts into perspective the correlation between the amazing COG Studies done and the Mechanism of Action..... https://www.jneurosci.org/cgi/content/full/27/11/2866#B44
.......Brain Hippocampal slices that had been exposed to Beta-Amyloid Oligomers showed Progressive Neuronal Cell Death and ultimately impaired electrical activity. AZD-103 was introduced and shown to restore the electrical activity every single time and this Analysis was repeated 1000 times.
Great quote here from Dr. Cruz........."Dr. Joanne Mclaurin (Inventor AZD-103) was looking at Neuronal Toxicity where Amyloid binds to Neuronal Cells and kills the Neuronal Cells and what she found was that if she added AZD-103 it PREVENTED the Neuronal Cell death. Then what she found was that to create Neuronal Cell death you need Fibrils (Oligomers) to come into contact with the Neurons. Just free Amyloid (Monomers) is not sufficient. What she found was that when she added AZD-103 was that it Broke Up the Fibrils." .......That's the simplest explaination yet for the Discovery of AZD-103/ELND005.
McLaurins Findings were put to the test and taken a few steps further to find the Mechanism of Action when it was shown that AZD-103 completely REVERSED Cognitive Impairment in a couple of separate but very different Cog Studies...... one of which was run by Dr. Selkoe. Remember that name! So then in the just recent Study 'Shankar et al 2007' (with Dr's. Selkoe, Walsh, Townsend etc.) showed that it prevents Synapes Loss!!
Anyone that hasn't read this study really should. It shows that Monomers (regular Amyloid) DO NOT cause Neuronal Cell Death!! Monomers display NO Neuronal Toxicity at all. What it does show is that when beta-Amyloid STARTS to Aggregate into Oligomers in the brain, specifically Dimers (2) and Trimers (3) in this study, that is when you can start to see the Dendritic Spine Loss and Neronal Cells Progressively Die and ultimately Synaptic Failure. This is when the memory starts going.
Furthermore, three other Studies support this.(Walsh et al., 2002; Cleary et al., 2005; Townsend et al., 2006a)........Wherein physiologically relevant levels of cell-derived beta-Amyloid Oligomers, but not monomers, acutely interrupt hippocampal synaptic plasticity in vivo and in slices and transiently impair learned behavior in rats. Recall the Lever Pressing Task ......In the Alternativing Lever Cyclic Ratio (ALCR) test rats must first learn a complex sequence of lever-pressing requirements in order to earn food reinforcement in a two-lever experimental chamber. Subjects must alternate between two levers by switching to the other lever after pressing the first lever enough to get food rewards. The exact number of presses required for each food reward changes, first increasing from 2 responses per food pellet up to 56 based on the quadratic function, x.sup.2-x. One cycle is an entire ascending and descending sequence of these lever press requirements (e.g., 2, 6,12, 20, 30, 42, 56, 56, 42, 30, 20, 12, 6, and 2 presses per food reward). Six such full cycles are presented during each daily session. Errors can be scored when the subject perseveres on a lever after pressing enough to get the food reward, i.e., does not alternate (a Perseveration Error), or when a subject switches levers before completing the response requirement on that lever (a Switching Error)......................
https://www.ncbi.nlm.nih.gov/pubmed/17192927?dopt=Abstract ............... So a Rat is trained to do this. Then beta-Amyloid Oligomers are introduced and the Rat can't do it anymore.....Then AZD-103 is given in drinking water and then the Rat CAN complete the task.
Oh...... and when the Shankar et al Scientists introduced AZD-103.......well it REVERSED the effects that the Beta-Amyloid Oligomers had on the Neuronal Cell Death and Dendritic Spine Loss and STOPPED Synaptic Failure in it's track. Bang !!