More Insight from the AAT-AD/PD Online Conference

Yesterday we posted some news on blood tests for Alzheimer's disease from the AAT-AD/PD online conference.  (The conference was held online due to the coronavirus pandemic.  Otherwise it would have been in Vienna, Austria.)  But there's more.

On February 16, we wrote about the failure of a couple of proposed drug interventions to improve cognition during Alzheimer's disease, including two candidate drugs named ganternerumab and solanezumab.  The news from the conference was that ganternerumab had been extraordinarily effective at removing beta amyloid (the type of amyloid associated with Alzheimer's disease) from the brain, and that it also removed pathologic tau protein.  There was an implication that, even though cognition didn't improve during the trials, it might improve given more time. 

The idea was that, after the amyloid plaques and tau are removed from the brain, it may be that the brain just needs time to heal afterwards.  Therefore, further testing is in order.

This was all discussed in an article in this week's ALZForum.

These conclusions may explain the results we discussed regarding the candidate drug BAN2401 back in July 2018.  BAN2401 needed further testing, but it appeared to improve cognition in Alzheimer's subjects if they remained on the drug for six months after the amyloid plaques had cleared.  With ganternerumab at least, and maybe with solanezumab, we have the bonus of clearing both the tau and the amyloid.

But there was a bonus in the ALZForum article.  About half-way down in the article was a graph that mapped the various dynamics of the disease progress.  The x-axis was a timeline beginning more than 20 years before the onset of symptoms (the beginning of MCI) and proceeding 10 years beyond.  "0" marked the onset of symptoms.  While it is very variable, five years in MCI and five years of Alzheimer's dementia ending in death is a possible scenario for an Alzheimer's patient.  We have noted before that the disease likely begins 20 years before any noticeable symptoms appear.

The graph displayed the rise of amyloid concentration in the cerebrospinal fluid, peaking at the 0 mark, and then declining gradually.  As we discussed previously, the later decline probably results from the amyloids beginning to agglomerate on the brain cells.  At the same time, the tau protein takes off right at the 0 mark -- when symptoms first appear.

The graph displays the decline of hippocampus volume, consistent with what my own MRIs have shown.  It also describes the decay in the ability of the brain to metabolize glucose.  It did not have an element describing the decline in brain volume, but that can be inferred from from the decline in hippocampus volume.  In my case, a hippocampus volume of <1 percentile for men my age corresponded with an increase in lateral ventricle volume to >99 percentile for men my age.  Those findings were from my MRIs in 2017 and 2018.  (The ventricles are void spaces in the brain that expand with the loss of brain volume, so it is an inverse proxy for loss of brain volume.)

I hope everyone stays safe during the pandemic!