Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease

Carter, Chris J.

Copper/aluminum Nanoparticles from aluminum, silver, or copper increase spinal cord pathology after trauma, an effect correlated with breakdown of the blood-spinal cord barrier [290] Diabetes mellitus BBB dysfunction plays a role in diabetes-associated neurological complications (stroke, vascular dementia, and cognitive deficits) [291] High intake of sugary drinks associated with preclinical markers of AD (memory and MRI measures) [292] Hyperglycemia impairs the integrity of the BBB [293] . Exercise in animal models of cerebral ischemia/stroke, diabetes, and brain metastasis has been shown to improve BBB function [301] . Physical activity counters the negative influence of PICALM, BIN1, and CLU risk alleles on episodic memory functioning in a dementia-free population [302] (all of these are expressed in the BBB proteome dataset) [ [309] . Bacterial LPS is disruptive in BBB models [310] Beneficial effects Anti-inflammatories (NSAIDS) and H2 histamine receptor antagonism Aspirin and celecoxib prevent disruption of the BBB in vesicular stomatitis virus-infected mice [311] . Dexamethasone and methylprednisolone as well as NSAIDs (ibuprofen and indomethacin) reduce vascular permeability in a rat glioma model [312] . Nimesulide (a selective cyclooxygenase-2 inhibitor) attenuates BBB disruption in animal models of cerebral ischemia [313] : Histamine causes BBB opening via H2 receptors and H2 receptor antagonism attenuates increased BBB permeability caused by hyperthermia in rats [314, 315]