Alzheimer’s and Amyloid

When thinking of ways you'd really like to avoid ending up in life, Rick and I agree on PodMed this week that developing Alzheimer's disease is close to the top of the list, in such salubrious company as ALS and locked in syndrome, and we're in abundant company.  Small wonder then, that research on Alzheimer's disease continues at a blistering pace on every aspect of the disease, with two papers representing four studies published in the New England Journal of Medicine this week on the use of antibodies against amyloid and their potential for helping folks with the disease.  Sigh.  That just about says it all with regard to these two drugs, at least in those disease stages in which they were tested.

Solanezumab and bapineuzumab are the names of these humanized mouse antibodies against beta-amyloid, with the former tested for its ability to reduce beta-amyloid in both plasma and cerebrospinal fluid, while the latter was assessed with regard to its ability to reduce beta-amyloid as seen with PET imaging as well as measurement of tau in the cerebrospinal fluid.  Patients enrolled in the former 2 trials were 55 years of age or older, had been diagnosed with mild to moderate Alzheimer's disease (AD) but without evidence of depression.  Subjects were randomized to 400mg of solanezumab received via IV infusion once every 4 weeks for a period of 18 months or placebo, with over 2000 people enrolled in these two studies. In the latter two trials involving bapineuzumab they also enrolled a couple of thousand folks with mild to moderate AD, aged 50 to 88 years.  They received either 0.5 or 1.0 mg per kilogram of the antibody or placebo via IV every 13 weeks for up to six infusions. Unfortunately neither drug had any impact on the cognitive and functional outcome measures used in these studies.  One group in the bapineuzumab study did show a reduction in CSF tau protein.  As I suggested at the outset, sigh.  While there are multiple reasons why antibody-mediated removal of beta-amyloid in people with mild to moderate AD might not work, it is disappointing. And it calls into question the hypothesis that accumulation of beta-amyloid is the key to the pathology of AD at all.  As has been suggested by others much more expert in this field than me, beta-amyloid may be a mere bystander in this arena and may only have utility as a surrogate for some other process that is so far, undefined.  Clearly, however, as the number of people who are projected to develop AD in the next couple of decades burgeons, as we are constantly refining ways to keep them alive longer, and the sheer number of healthcare providers who are needed to take care of these folks is projected to be huge while the supply is too small, we are headed for a train wreck.  For the moment I will cite Constantine Lyketsos, an AD expert here at Johns Hopkins, who says that while waiting for an effective treatment or preventative, make healthy choices with regard to diet and exercise, don't smoke, and stay socially engaged.

Other topics this week include risks of off-hours heart attack in the BMJ, MS and vitamin D levels in JAMA Neurology, and access to firearms, homicide and suicide in Annals of Internal Medicine.  Until next week, y'all live well. And for those who want to get automatic updates on their smartphone or other device of the podcast, here's the new link so  you can update:

https://itunes.apple.com/us/podcast/johns-hopkins-medicine-media/id792911349?mt=2

Happy listening!

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4 Comments

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Julia February 5, 2014 at 12:07 am

What happened to the PodMed podcast? I used to love it... now it is 1-minute pointless blurbs... please tell me I am wrong and that you guys (Elisabeth and Rick) are not off the air!

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Elizabeth Tracey February 5, 2014 at 9:25 am

https://itunes.apple.com/us/podcast/johns-hopkins-medicine-media/id792911349?mt=2

hey, Julia, here is the correct link. Happy listening! and many thanks for writing

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Barb January 26, 2014 at 11:52 am

How about reactivating PodMed on the Stitcher app? It dropped off several months ago...Stitcher is really handy for android tablets.

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Elizabeth Tracey January 27, 2014 at 9:37 am

Barb, thank you for your comment. We are working to migrate all the content to a much more accessible and integrated website soon, so please stay tuned. Thank you for writing.

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