Considering the Choroid Plexus in Alzheimer's Disease
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Amyloid levels in the brain are very dynamic, capable of changing rapidly. That amyloid builds up with age to contribute to the development of neurodegenerative conditions such as Alzheimer's disease points to a slow breakdown in the balance of generation and clearance. The choroid plexus is a filtration system for cerebrospinal fluid, and hence a place to look for failures, such as a progressive loss of the protein machinery needed to extract amyloid from the brain:

Accumulation of amyloid-beta peptides (Aβ) results in amyloid burden in normal aging brain. Clearance of this peptide from the brain occurs via active transport at the interfaces separating the central nervous system (CNS) from the peripheral circulation. The present study was to investigate the change of Aβ transporters expression at the choroid plexus (CP) in normal aging.

Morphological modifications of CP were observed by transmission electron microscope. Real-time RT-PCR was used to measure mRNA expressions of Aβ42 and its transporters, which include low density lipoprotein receptor-related protein-1 and 2 (LRP-1 and -2), P-glycoprotein (P-gp) and the receptor for advanced glycation end-products (RAGE), at the CP epithelium in rats at ages of 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months. At the same time, the mRNA expressions of oxidative stress-related proteins were also measured.

The results showed that a striking deterioration of the CP epithelial cells and increased Aβ42 mRNA expression were observed in aged rats, and there was a decrease in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE mRNA expression and an increase in LRP-2, the CP epithelium Aβ influx transporter. These results suggest the efficacy of the CP in clearing of Aβ deceases in normal aging, which results in the increase of brain Aβ accumulation. And excess Aβ interferes with oxidative phosphorylation, leads to oxidative stress and morphological structural changes. This in turn induces further pathological cascades of toxicity, inflammation and neurodegeneration process.

Link: http://www.ncbi.nlm.nih.gov/pubmed/24777406

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