I am trying to understand the relationship between the healthy aging process and the development of the blood brain barrier disruption which might lead to several neurodegenerative diseases such as Alzheimer's disease.
Finding a cure for such complicated diseases requires a good understanding of the underlying mechanisms that lead to the development of the disease and a healthy blood brain barrier plays a major role in preventing such diseases.
Aging and BBB dysfunction is an interesting topic because its a high risk factor for developing neurodegenerative diseases. To my knowledge most of recent studies point at loss of tight junction proteins of the BBB with aging which is likely due to neuroinflammation. Infiltration of circulatory leukocytes and blood borne immunoglobines into the brain is a marker of BBB leakage that happens in aged humans. In aged mice however, only loss of TJ proteins of BBB was observed. I think its not clear which come first, neuroinflammation or BBB leakage. It could be systemic inflammation disrupts the BBB first and lead to infiltration of toxins to the brain that trigger neuroinflammation. Not sure if the brain itself with aging would autonomously initiate inflammation due to certain malfunctioning in metabolic processes and clearance pathways to remove waste byproducts !?.. I would love to here comments from experts in the field..
The following reference might help: Montagne et al. Neuron. 2015 Jan 21;85(2):296-302
On the last published research article we point out the importance of methemoglobinemia not only as the biomarker and precursor of the effects of environmental oxidants, but a carrier and donor of redox-active ferric iron. We identify ferric iron as an originator having an important role in crossing brain microvessels
to neurons (neurovascular unit), causing neuronal death and continous
ageing process, and leading finally to hard neurodegenerative disorders
such as AD, PD, MS and other diseases.
More about that argument you can find upon link.
http://dx.doi.org/10.4172/2380-2391.1000169
Greater levels of AD pathology seem to be associated with greater levels of BBB leakiness http://www.ncbi.nlm.nih.gov/pubmed/21970975
Dear Robin , your observetion just confirm my research statement which contribute to explain the mechanisms leading to BBB leakage in brain ageing process and its relationship to Alzheimer's -type pathology progression.
Montagne et al. Neuron. 2015 Jan 21;85(2):296-302 is a crucial reference on the topic. A possible relation between aging and BBB dysfunction may also be endothelial senescence.We observed (Although our interest was to study microglia)changes in the endothelial layer and BBB in the mTerc mouse model. Refer https://www.researchgate.net/publication/280912607_Enhanced_microglial_pro-inflammatory_response_to_lipopolysaccharide_correlates_with_brain_infiltration_and_blood-brain_barrier_dysregulation_in_a_mouse_model_of_telomere_shortening
Article Enhanced microglial pro-inflammatory response to lipopolysac...
Thank you all for your informative answers
best wishes
Sweilem
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