July 24, 2012

Alzheimer's and Diabetes: More Links

We’ve known for years about the apparent link between Alzheimer's disease (AD) and diabetes. A quick scan for articles in the e-journal Science Daily shows the recent history:
I’ve recently seen several new reports about this link. Both expand the science that is inexorably revealing the nature of the connection between the two diseases, thus increasing the likelihood of new treatments – even cures -- for both conditions.

Dementia Gene Affects Insulin Pathway
As reported in the June 2012 edition of the journal "Genetics," researchers at The City College of New York (CCNY) have isolated a single gene associated with AD and diabetes, which gives scientists a new target for treatment.

That gene affects the insulin pathway. Said Biology professor Chris Li, “People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy.”

In their investigation, the CCNY team used a common research tool: the free-living, non-parasitic soil nematode worm Caenorhabditis elegans (C. elegans). Li and her group found that a gene in the worm closely resembled a human gene associated with AD. The scientists found the worm gene in various metabolic pathways, including the insulin pathway. Referring to the neuron-destroying amyloid plaques typically found in the brains of people with AD, Li said:
Mutations in three genes, including the amyloid precursor protein (APP) gene, have been correlated with the inherited form of Alzheimer’s disease in humans. Because the equivalent gene we’re studying in the model organism C. elegans is involved in many metabolic pathways, it suggests that the human version of the gene likely also plays a role — not only in Alzheimer’s disease, but in diabetes as well.
Genetics editor-in-chief Dr Mark Johnston said:
This is an important discovery, especially as it comes on the heels of the U.S. government’s new commitment to treat and prevent Alzheimer’s disease by 2025. We know there’s a link between Alzheimer’s and diabetes, but until now, it was somewhat of a mystery. This finding could open new doors for treating and preventing both diseases.
Of course, more research and testing are necessary – and with humans, not worms – before we can get too excited about this finding.

Does Untreated Diabetes Provide a Physiological Model for AD's Development?
The second report, published last week in the Journal of Alzheimer’s Disease, was featured in the July 19 edition of the e-journal Human Health and Science. Researchers from the University of Medicine and Dentistry of New Jersey (UMDNJ), in concert with scientists from Northwestern University in Illinois, asserted that untreated diabetes provides a workable physiological model for AD neuropathology.

Researchers found increased amyloid beta peptides in the brain cortex and hippocampus of people with untreated diabetes. Accumulation of those substances – which eventually disrupt the normal functioning of neurons -- is a hallmark of the AD brain.

The scientists also studied the retinas of people with diabetes, and found amyloid buildups in these eye tissues similar to the customary accretions found in the brains of people with AD. No comparable accumulations were discovered in retinas of people without diabetes.

UMDNJ researcher Peter Frederikse, PhD, said, “"Our findings indicate that scientists may be able to follow the onset and progression of Alzheimer's disease through retinal examination, which could provide a long sought after early-warning sign of the disease."

Research has shown that insulin plays a role in memory formation. When amyloid structures attach to neurons, the neuro-toxins cut off insulin receptors, eventually producing insulin resistance in the brain. Developing diabetes then creates denser amyloid accumulation, making neurons even more insulin resistant. It’s a vicious cycle, in which diabetes and memory impairment develop concurrently, from the same cause.

It’s no wonder that we’re seeing widespread increases in both diseases, given their causal links. Said researcher Chinnaswamy Kasinathan, PhD,
In light of the near epidemic increases in Alzheimer's disease and diabetes today, developing a physiological model of Alzheimer neuropathology has been an important goal. It allows us to identify a potential biomarker for Alzheimer's disease and may also make important contributions to Alzheimer drug testing and development.

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