A dysfunction in the lining of blood vessels causing cardiovascular illness is also involved in the development of Alzheimer's disease, reports a new study.
Two distinct anomalies in the brain are hallmarks of Alzheimer's: neurofibrillary tangles, twisted fibres composed primarily of a protein called tau that arise inside nerve cells, or neurons; and amyloid plaques, a buildup between neurons of protein fragments called amyloid beta peptides.
Previous research has found that people with multiple cardiovascular risk factors are also at greater risk for Alzheimer's.
"If you look at any risk factor for cardiovascular disease - the standard risk factors like high cholesterol, diabetes, hypertension, smoking, sedentary lifestyle, aging - all of these have been associated with loss of nitric oxide in the endothelium, a condition known as endothelial dysfunction," said Zvonimir S. Katusic, senior author of the study.
In the study, the researchers tested whether endothelial dysfunction also plays a role in Alzheimer's disease.
Using endothelial cells from microscopic blood vessels in the human brain, the scientists chemically inhibited eNOS (endothelial nitric oxide synthase), an enzyme involved in nitric oxide production.
Inhibition of eNOS triggered a series of biochemical effects that led to an increase in the production of amyloid precursor protein (APP), the raw material for the amyloid plaques seen in the brains of Alzheimer's patients.
The quantity and activity of BACE1 also increased. BACE1 is an enzyme that cleaves APP to create the amyloid beta peptides that make up the plaques.
The research team also studied tiny blood vessels in the brains of mice that had been genetically engineered to lack the eNOS enzyme.
Those mice - which naturally have higher blood pressure and are prone to insulin resistance compared with normal mice - had about a 50 percent reduction in nitrates and nitrites which indirectly reflect nitric oxide production. The eNOS-deficient mice also showed higher levels of amyloid beta peptide in the brain, along with more APP and BACE1.
The study has suggested that preserving a healthy blood vessel wall is important in preventing cognitive impairment and ultimately Alzheimer's disease, said Katusic.
"On the cardiovascular side we've known for some time that preservation of healthy endothelium is critical to prevent major cardiovascular events. Now it seems this may have important implications for cognitive impairment," he said.
The study was published in Circulation Research: Journal of the American Heart Association.