Another Post-Amyloid Possibility?

We have been less than enthusiastic about all of the research attention going to "the amyloid hypothesis."  Other factors, like viruses, bacteria, and genetics cause and/or contribute to both the initiation and progress of Alzheimer's disease.  Some of these factors may turn out to be more productive targets of research.  There may be interventions that are more effective than simply removing beta amyloid from the brain, but that's where most of the attention has been.  

Our friend Laurie directed me to some very interesting new research that has popped up from MIT’s Picower Institute for Learning and Memory, published in the Proceedings of the National Academy of Sciences.  The research suggests that interfering with the activities of a certain enzyme in the brain, which is overactive in Alzheimer's disease, could actually reverse the effects of the disease.

The news is exciting, but we are very early on the path to development of an actual treatment from this research.  And the current research has been conducted with genetically modified mice.  The mice have been bred to have brains that behave much like human brains with Alzheimer's disease.  But as we've noted before, promising research with these mice has often led to disappointment.  That's because mice aren't people.

But it is still exciting.  Essentially, the researchers treated mice with a peptide that blocks the operation of a certain version of an enzyme leading to dramatic reductions in neurodegeneration and DNA damage in the brain.  The enzyme has been implicated in the tau tangles that we discussed in Beating the Dementia Monster and are typical of the progress of Alzheimer's disease.  After treatment, the mice showed improvements in their ability to perform certain tasks, like learning to navigate a maze.

What's a peptide?  What's an enzyme?  A peptide is a string of amino acids, usually strung together inside a cell to build a protein.  Chains of peptides are then shaped into proteins.  Which amino acids are in a given string (and therefore the protein) is specified by the corresponding gene in the DNA.  Some peptides, like beta amyloid, may not be long enough to form an actual protein.

An enzyme is a protein that, due to its size, shape, and arrangement of charges, catalyzes chemical reactions.  For example, the burning of carbon and hydrogen in your body (taken from the food you ate) takes place at much lower temperatures than in your fireplace, because the reactions are catalyzed by enzymes.  Enzymes do a lot of really important stuff in biochemistry, especially in the brain.

The enzyme in question here is called CDK5, and it regulates synaptic function.  Sometimes ... maybe not so well.  There have already been efforts to moderate the activity of CDK5 in Alzheimer's disease, but these efforts have not gone well.  The researchers believe that using a certain artificial peptide, rather than the drugs that were tried earlier, is producing much more promising results.  The special peptide was engineered by the researchers with 12 amino acids in the chain.

So will this turn out to be a whole new path to a truly effective treatment?  It certainly has the potential.