Role of Blood-Brain Barrier in Alzheimer’s Disease

Abstract

The blood-brain barrier (BBB) is involved in the pathogenesis of Alzheimer's disease (AD). BBB is a highly selective semipermeable structural and chemical barrier which ensures a stable internal environment of the brain and prevents foreign objects invading the brain tissue. BBB dysfunction induces the failure of Aβ transport from brain to the peripheral circulation across the BBB. Especially, decreased levels of LRP-1 (low density lipoprotein receptor-related protein 1) and increased levels of RAGE (receptor for advanced glycation endproducts) at the BBB can cause the failure of Aβ transport. The pathogenesis of AD is related to the BBB structural components, including pericytes, astrocytes, vascular endothelial cells, and tight junctions. BBB dysfunction will trigger neuroinflammation and oxidative stress, then enhance the activity of β-secretase and γ-secretase, and finally promote Aβ generation. A progressive accumulation of Aβ in brain and BBB dysfunction may become a feedback loop that gives rise to cognitive impairment and the onset of dementia. The correlation between BBB dysfunction and tau pathology has been well-reported. Therefore, regulating BBB function may be a new therapeutic target for treating AD.

Combinatorial analyses reveal that cellular composition changes have different impact on transcriptomic changes of cell type specific genes in Alzheimer’s Disease brains

“…AD2 is linked to gliogenesis and cell motility. N8 is involved in gap junction, which supports the assumption that gap junction associated with blood brain barrier may be disrupted in AD to allow the access of virus or bacteria to AD brain (Cai et al, 2018;Devanand, 2018;Montagne et al, 2017;Readhead et al, 2018).…”

Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

“…In fact, EVs shed from CNS neurons and glia can be found in peripheral blood and in tears [44,205], particularly when inflammatory mediators activate CNS endothelia, enhancing BBB permeability [206,207]. In this regard, it has been observed that the permeability of the BBB is increased in neurodegenerative conditions such as Alzheimer's disease, vascular dementia, and multiple sclerosis [45,[208][209][210]. Furthermore, systemic inflammation increases BMEC permeability and modulates BBB functions [207,211,212].…”

G protein‐coupled oestrogen receptor stimulation ameliorates iron‐ and ovariectomy‐induced memory impairments through the cAMP/PKA/CREB signalling pathway

“…Neurodegenerative diseases such as AD are complex multifactorial pathologies, emerging from a multitude of alterations that include oxidative stress, protein aggregation, energetic failure, synaptic dysfunction and inflammation, which ultimately lead to cell death in specific brain regions . Disruption of iron homeostasis and consequently its accumulation has been associated with the pathogenesis of neurodegenerative disorders, such as Parkinson's disease (PD) and AD .…”

“…15 Neurodegenerative diseases such as AD are complex multifactorial pathologies, emerging from a multitude of alterations that include oxidative stress, protein aggregation, energetic failure, synaptic dysfunction and inflammation, which ultimately lead to cell death in specific brain regions. 17,18 Disruption of iron homeostasis and consequently its accumulation has been associated with the pathogenesis of neurodegenerative disorders, such as Parkinson's disease (PD) and AD. 19 Recently, it was suggested that exposure to high levels of iron during childhood increases susceptibility to neurodegenerative diseases such as PD and AD in elderly, considering a "window of vulnerability" in which, during the first 2 years of life, the blood-brain-barrier is more accessible to iron levels in the periphery leading to iron over storage in the brain.…”