Brain Metabolism, Alzheimer's

I found this HHMI research into brain metabolism and Alzheimer's rather interesting, especially in light of another recent piece on changes in gene expression in the aging brain. Alzheimer's disease appears to be like rust - you can certainly put it off, you may be lucky enough to have moderately rustproof genes, but live long enough and you'll get it eventually ... and it will kill you. All common neurodegenerative conditions are high up on the healthy life extension hit list - we need to have cures or preventions if progress elsewhere in the science of living longer is to benefit us.

Alzheimer's may be a natural consequence of normal ongoing metabolic processes, and we all know by now that neither "natural" nor "normal" necessarily means "good," I trust. Different parts of the brain have different levels of usage, and those areas with greater usage may lapse into Alzheimer's more quickly:

The availability of powerful imaging techniques and the ability to merge different sets of imaging data through new bioinformatics and statistical methods enabled Buckner and his team to construct a picture of Alzheimer's from molecular changes to the structural and functional manifestations of the disease. In the process, the team unexpectedly observed that the regions of the brain that light up when we slip into comfortable patterns of thought are the same as those that, later in life, exhibit the disabling clumps of plaque characteristic of Alzheimer's, a disease that most frequently manifests itself after age 60.

That remarkable correlation, said Buckner, suggests that dementia may be a consequence of the everyday function of the brain.


The default state, according to Buckner, is characterized by metabolic activity in specific regions of the brain, notably the posterior and cortical regions. "These regions were active in the default states in young adults and also showed amyloid (plaque) deposition in older adults with Alzheimer's disease," the researchers write in the new Journal of Neuroscience paper.

"The key insight is that brain activity and metabolism are not uniform across the brain," Buckner said. "When we looked at people on the cusp of dementia, we saw a loss of brain tissue in the regions we predicted it would occur," based on our observations of metabolism.


Buckner emphasized that the notion of a causative relationship between everyday metabolic functions of the brain and Alzheimer's remains a hypothesis. However, new studies may help "show if amyloid (plaque) deposition is really dependent on metabolism. Can we find a biologically plausible reason for how metabolism causes Alzheimer's disease?"

Food for thought, and possibly groundwork for the second generation of effective therapies. The first generation of effective therapies for Alzheimer's is likely to be based on gene therapy to tailor the immune system into cleaning up the damage - that will work, or so it seems from early stage studies, but prevention is always better than a cure.


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