A paradigm reversal in Alzheimer's disease ?

[Peter Cobbold]

Most forumites will have experienced family members or friends suffering Alzheimer's Disease, and wondering when drugs might be available. For the past three decades a paradigm has won near-consensus amongst researchers that aggregation of two brain proteins, amyloid and tau, were causing disease. Experiments to lower aggregation have succeeded , BUT failed to slow the disease and some even made dementia worse. This week a paper by Espay et al begins to overturn the "proteinopathy" paradigm by showing pts with more soluble amyloid were spared dementia. After 30 years it opens up new approaches. An overview is here:

https://medicalxpress.com/news/2021-06-prevailing-alzheimer-theory-discovery.html

This is the very  stuff of science !!

Peter

 

 

[cvtrian]

Thanks Peter, fingers crossed for some real progress against this disease
Ian

[Peter Cobbold]

35 minutes ago, cvtrian said:

Thanks Peter, fingers crossed for some real progress against this disease
Ian

Ian, Yes, indeed. It opens up a whole new approach which is encouraging.  But looking at what amyloidB and tau might do physiologically leads to no clear insights, they appear to do lots of diverse things. The genes can be traced back 500 miilion years, suggesting fundamental role(s).  https://link.springer.com/article/10.1007/s00401-020-02196-w

It will take time. The big problem with brain research, which is why it takes so long, is that researchers cant take biopsies.

Peter

 

[Nigel Triumph]

Thank you Peter, fascinating.

It's too late for many Alzheimer's patients of course, including my mother but it certainly offers new hope for future generations.

Nigel

[john.r.davies]

Meanwhile, the paradigm that AD is caused by amyloid plaques continues to hold the administrators in thrall.   The FDA ha approved the use of Aducanumab, an antibody against plaque, despite the only studies being very small indeed, and with only marginal success.

And like other drugs of this type, it's very expensive, about $56K a year, per patient.

[AndyR100]

If interested, worth watching the progress of Donanemab which was recently granted Breakthrough Therapy designation by the FDA.

[john.r.davies]

Indeed, Andy!    And maybe a final test of the Amyloid Theory, that has been paramount for so long, without any other evidence that drugs to combat plaques are effective. But neither Donanemab (See: https://pubmed.ncbi.nlm.nih.gov/33720637/) or aducanumab (See:  https://pubmed.ncbi.nlm.nih.gov/33135381/) have been found to have anything more than marginal improvements. As Peter says, we need new thinking.   

John

[Peter Cobbold]

It's snowing new insights !  Parkinson's diseases are second only to Alz in prevalence. The culprit appears to be toxic aggregations of a molecule that makes up 1% of the  brains protein : synuclein. This week it has been discovered by Spanish resarchers that, out of thousands of molecules tested one is especially good at stopping synuclein from aggregating.  LL37.   Sounds familiar? LL37 is a fragment of cathelicidn that is an anti-microbial peptide important in innate immunity ( see the coronavirus thread).  D3 promotes expression of cathelicidin. Fascinating. The function of synuclein is not known. But is has a structure that resembles cathelicidin !  It may be that PD  reflects innate immunity goen out of control in the brain. Its still a complicated mess to unravel, but does to me point to the desirability of supplementing with D3 life-long. Why? rural dwelling elderly Kenyans do not get age-related PD, and thay have serum 25(OH)D levels, from year round sun, double or treble UK.  

The ducks are far from all being in a row, but they are providing clues that  should speed up understaning and thence interventions. Quackery it aint.

Peter

[Peter Cobbold]

6 hours ago, john.r.davies said:

Indeed, Andy!    And maybe a final test of the Amyloid Theory, that has been paramount for so long, without any other evidence that drugs to combat plaques are effective. But neither Donanemab (See: https://pubmed.ncbi.nlm.nih.gov/33720637/) or aducanumab (See:  https://pubmed.ncbi.nlm.nih.gov/33135381/) have been found to have anything more than marginal improvements. As Peter says, we need new thinking.   

John

 

https://scienceofparkinsons.com/2021/06/08/arukindingmab/