More on Alzheimer's and Tight Junction Alterations
The tight junctions between cells of the blood brain barrier are a part of the system controlling passage of molecules between the blood system and brain tissue. They appear to change and fail with age, and this may be one of the ways in which ongoing clearance of amyloid-β falters, allowing the buildup of amyloid associated with Alzheimer's disease. Equally some of the changes may be due to increased but still insufficient efforts at clearance via this mechanism due to the failure of other, primary modes of clearance:
Alzheimer's disease is characterized, in part, by the build-up of a small protein ('amyloid-beta') in the brains of patients. Impaired clearance of this protein appears to be a major factor in the build-up of plaques, and then in the disease process itself. While the mode by which amyloid-beta is cleared remains unclear, it is evident that it needs to be removed from the brain via the bloodstream.Unlike blood vessels anywhere else in the body, those in the brain have properties that strictly regulate what gets in and out of the delicate tissue - this is what is known as the blood-brain barrier (BBB). The BBB functions as a tightly regulated site of energy and metabolite exchange between the brain tissue and the bloodstream. "We have shown that distinct components of these blood vessels termed tight junctions are altered in Alzheimer's disease. We think that this alteration could be an entrained mechanism to allow for the clearance of toxic amyloid-beta from the brain in those living with Alzheimer's disease."
The researchers examined brain tissues of individuals who were affected by Alzheimer's disease during their lifetime and then compared results to those observed in model systems in the laboratory. "Our recent findings have highlighted the importance of understanding diseases at the molecular level. The concept of periodic clearance of brain amyloid-beta across the BBB could hold tremendous potential for Alzheimer's patients in the future. The next steps are to consider how this might be achieved. Given the recent advances in clinical trials of anti-amyloid beta antibodies, we hope our findings may lead to improved and adjunctive forms of therapy for this devastating condition."
Link: http://www.eurekalert.org/pub_releases/2015-09/tcd-trr091715.php