The blood-brain barrier is a lining of specialized cells that surrounds blood vessels passing through the brain. The barrier permits only certain molecules and cells to pass, isolating the tissue environment of the brain from that of the result of the body. When the blood-brain barrier leaks, an immediate consequence is inflammation in brain tissue, the result of the brain’s immune cells reacting to the presence of inappropriate molecules. Unfortunately the integrity of the blood-brain barrier degrades with age and the accumulation of molecular damage, as is the case for all other tissues. The resulting inflammation is an important mechanism in the progression towards neurodegenerative disease and dementia. As noted here, degradation of the blood-brain barrier may also prevent necessary molecules from being transported into the brain in sufficient amounts. That also may be an important early determinant of loss of function in brain tissue.
The vascular endothelium in the brain is an essential part of the blood-brain-barrier (BBB) because of its very tight structure to secure a functional and molecular separation of the brain from the rest of the body and to protect neurons from pathogens and toxins. Impaired transport of metabolites across the BBB due to its increasing dysfunction affects brain health and cognitive functioning, thus providing a starting point of neurodegenerative diseases.
The term “cerebral metabolic syndrome” is proposed to highlight the importance of lifestyle factors in neurodegeneration and to describe the impact of increasing BBB dysfunction on neurodegeneration and dementia, especially in elderly patients. If untreated, the cerebral metabolic syndrome may evolve into dementia. Due to the high energy demand of the brain, impaired glucose transport across the BBB via glucose transporters as GLUT1 renders the brain increasingly susceptible to neurodegeneration. Apoptotic processes are further supported by the lack of essential metabolites of the phosphocholine synthesis.
In Alzheimer’s disease, inflammatory and infectious processes at the BBB increase the dysfunction and might be pace-making events. Chronic inflammatory processes of the BBB transmitted to an increasing number of brain areas might cause a lasting build-up of spreading, pore-forming β-amyloid fragments explaining the dramatic progression of the disease.