Biogen, Anavex, PBT, page-17

Well-said. I was briefly on the Yahoo message board but left it due to all the mud slinging. I came here because I didn't have to sort through all that and was just able to read the studies along with good analysis of those studies. Maybe it is easier for me as I have no financial stake either way. All I want to do is to understand the disease and how to treat it, in part because two of my relatives died from Alzheimer's disease and my mother had it for eight years before dying from heart failure.

Belatedly, I thank ITM for the great roundup following the Alzheimer's international conference. In my mind, it should now be clear that removing amyloid plaques does not provide any benefit. Early this year, Biogen played with numbers to make the results look significant but the results from the 6mg group at one year was really the end for their drug. Lilly is limping along but that its researchers had to work so hard to squeeze out even a hint of efficacy is yet more evidence that amyloid plaques do not cause Alzheimer's disease.

Amyloid oligomers are more problematic in that they do contribute to oxidative damage but that damage mainly ends when copper and zinc are entombed in plaques.

The anti-tau drugs should not fare much better. Tau only becomes a problem when it becomes nitrated by peroxynitrites or via transition metals. As long as the body's antioxidant systems are not depleted, individuals can have both amyloid and tau and be cognitive all right.

So now the field is reduced to this, drugs that alter the compounds and pathways that lead to oxidation and neuronal cell death. One is PBT2 because it inhibits the formation of inducible nitric oxide that combines with superoxide anions to form peroxynitrites. The other is Anavex because it inhibits NMDA receptor activity that leads to peroxynitrites in middle to late Alzheimer's disease. Here is some interesting information regarding sigma 1 agonists (such as the combination of Aricept and Anavex):

In fact, those drugs were able to attenuate the cell loss observed in the CA1 pyramidal neuron layer of the hippocampus, the astroglial reaction measured by increase in GFAP immunolabeling in the cortex and hippocampal hilus, the induction of oxidative stress measured by increase in lipid peroxidation or protein nitration in the hippocampus, the induction of the expression of caspase-12, a marker of the endoplasmic reticulum stress, or caspase-3, a marker of apoptotic processes (Meunier et al., 2006b; Villard et al., 2009).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785038/

If you combine several of these drugs (PBT2 and Anavex, for instance) that inhibit oxidation and nitration with compounds that partially reverse oxidation and nitration then you likely have a winner.