Remarkable Study Links Mechanisms behind Alzheimer's and Down's

Thanks to Bio.com for a report on research findings that may suggest treatments for Alzheimer's Disease, as well as for Down's Syndrome and other forms of mental retardation.

A new UCLA/Veterans Affairs study implicates defects in the machinery that creates connections between brain cells as responsible for the onset of Alzheimer disease.

The defect in PAK enzyme signaling pathways -- vital to creation of these connections, or synapses -- is related to loss of a synapse protein in certain forms of mental retardation, such as Down syndrome. The new finding suggests therapies designed to address the PAK defect could treat cognitive problems in both patient populations.

...This new study implicates the PAK enzyme-signaling pathway, which is known to play a role in synapse formation and developmental cognitive deficits, or mental retardation.


The PAK enzymes form a family that includes two members known to localize to synapses (PAK1 and PAK3). Both are known to play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. Both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients to an extent sufficient to contribute to cognitive decline.

The research team finds that blocking these PAKs in middle-aged mice causes memory loss together with deficits in a protein involved in making neuronal connections. In humans, the same protein shows large losses in Alzheimer as well as in Down syndrome, the most common cause of mental retardation.

It is interesting to think of Down's syndrome as an ongoing process like Alzheimer's, rather than a "set in stone" condition. In other words, in spite of the chromosomal defect (trisomy21) of Down's syndrome, effective treatments might still be developed for the cognitive aspects of the disease by treating the underlying mechanism of the cognitive problems. Can you imagine millions of "Flowers for Algernon" scenarios playing out in families around the world? At both ends of the age spectrum? It is amazing to contemplate.

This study even ties into the theory of Abeta 42 (sticky protein) causation of Alzheimer's, since it was found that oligomers of Abeta42 caused similar types of defects in PAK as those found in Alzheimer's.