To follow up on comments on the culture of Alzheimer's research linked over at the Longevity Meme, I thought I'd point out some of the folk working hard to inject new ideas and theories into the field. You don't have to look far; quite a few interesting lines of research have reached the popular science websites in just the past few days:
Scientists have discovered how heart disease or a stroke may trigger Alzheimer's disease. Both conditions lead to a reduction of oxygen flow to the brain. A University of British Columbia team, studying mice, found this stimulates increased development of the protein clumps thought to cause Alzheimer's.
Scientists have known for some time that people with certain diseases that restrict their supply of oxygen, such as stroke or lung disorders, are more prone to Alzheimer's and also that people who live at high altitudes are also at greater risk of developing the disease. This research provides a molecular explanation for that anecdotal finding and shows that cues from cells, genes and a person's environment all play a role in causing this dreadful disease.
The study uncovers how cholinergic neuronal circuits, which help the cerebral cortex process information more efficiently, rely on neurotrophin-3, a chemical that stimulates nerve growth. The scientists have determined the circuits need this chemical in order to recognize and reach their target nerve cells in the brain.
This finding, according to Robertson, has significant implications for neurodegenerative diseases like Alzheimer’s. Cholinergic neuronal circuits play a key role in the proper information processing by the cerebral cortex and other areas of the brain. The cerebral cortex is the part of the brain that determines intelligence, personality, and planning and organization, and these actions are compromised by neurodegenerative diseases.
“Studies on the brains of Alzheimer’s patients have shown a marked decline in these cholinergic circuits. Our work demonstrates that neurotrophin-3 is essential to maintain the connections to cerebral cortex neurons,” Robertson said. “This study shows that a neurotrophin-3 therapy may be able to induce nerve fibers to regrow in the cerebral cortex, which would be beneficial to people with Alzheimer’s.”
A peacekeeper in the body's defenses against infection may hold the key to understanding - and eventually treating - Alzheimer's disease. Researchers at the Stanford University School of Medicine discovered that when a molecule responsible for dialing down the immune system malfunctions in the brain cells of mice, the rodents develop symptoms of the degenerative brain disease.
Wyss-Coray and Ina Tesseur, PhD, an instructor in the Department of Neurology, examined thin slices of the brains of Alzheimer's patients who had died, and discovered abnormally low levels of a molecule involved in controlling the body's response to infection. That molecule allows the brain to detect and respond to TGF-beta, or transforming growth factor, a protein teeming through our bodies, involved in fighting infection, stopping cancer and perhaps keeping brain cells alive.
No other researchers had seen this change before, so Tesseur and Wyss-Coray set out to investigate whether it had some connection to Alzheimer's disease. They hypothesized that by protecting neurons, TGF-beta may help prevent Alzheimer's disease. If the TGF-beta pathway is turned off, the brain becomes more susceptible to a toxic buildup of proteins.
The problem with Alzheimer's - and most other complex biochemistry - is the matter of identifying what is the cause and what is the effect. It is to be expected that much of what has been discovered by researchers will fall to the wayside as a side-effect of the progression of Alzheimer's rather than an actual root cause. Equally, most of the therapies currently under development will turn out to be largely ineffective patching up of consequences rather than cures. Such is the way we forge into the unknown; understanding will come, as the scientific method is a powerful filter for effective solutions to any problem.
Is Alzheimer's actually a form of diabetes at root? Is it a failure of amyloid clearing mechanisms? Is amyloid even a cause, or is it a giant red herring and consequence of the real underlying biochemistry of the condition? It's a complex business - new ideas and broader exploration are certainly needed while the establishment forges ahead with consensus work on understanding and defeating the buildup of amyloid.