Alzheimers Plaques Inhibit Compound Important for Brain Blood Flow


Levels of nitric oxide (NO), a signaling protein that helps regulate blood flow and neurological processes, are known to be low in the brains of people who have Alzheimer’s disease. New research into this process has discovered how the characteristic beta-amyloid plaques of patients with Alzheimer’s interact with this compound and inhibit this important biological pathway.

Amyloid-Beta Plaques Interrupt Nitric Oxide Production in Brain

Nitric oxide is now considered a neurotransmitter that is not stored in the synapses, but instead synthesized as needed by NO synthase (NOS), an enzyme, from its precursor L-arginine, a protein. It is broadly localized in the central nervous system, where it contributes to learning and memory mechanisms.

NOS may also be neuroprotective during amyloid-beta induced cell death.

Read: Pine Bark Extract A Potent Antioxidant

A research team led by Thomas Miller PhD and David D. Roberts PhD, both of the Laboratory of Pathology at the National Institutes of Health, studied both mouse and human cells that contained amyloid-beta, the main component of the plaques that accumulate in the brain cells of patients with Alzheimer’s disease.


They found that amyloid-beta binds to a cell surface receptor called CD36, which causes decreased activity of enzymes and reduces NO signaling. This inhibition in normal signaling interrupts blood flow to the brain.

But that inhibitory effect required interaction of CD47, another cell surface protein. This indicates to the researchers that there are additional steps in the biological pathway that remain to be identified.

Read: Lysosome Dysfunction May Be Key to Alzheimer's Disease Pathology

Jeffrey S. Isenberg MD MPH, study co-author and associate professor at the University of Pittsburgh School of Medicine, says that identifying how amyloid-beta inhibits the NO signaling pathway can lead to the development of a therapeutic agent to slow Alzheimer’s disease progression.

He adds, "There is evidence that suggests enhancing NO levels can protect neurons from degenerating and dying.”

Source Reference:
Miller TW, Isenberg JS, Shih HB, Wang Y, Roberts DD, 2010 Amyloid-β Inhibits No-cGMP Signaling in a CD36- and CD47-Dependent Manner.PLoS ONE 5(12): e15686. doi:10.1371/journal.pone.0015686