Week 6: The Cholesterol Question

Apr 24, 2020

Welcome back, everyone! It’s been another successful week researching as I began to re-investigate my research question using the information I had learned from the past two weeks. I realized that cardiovascular abnormalities (if they were to ever precede cognitive decline) would occur many years before the onset of AD itself. But this is not necessarily a concern. As was shown in my posts over the past two weeks, amyloid deposition precedes the emergence of AD by about 15-20 years. If cardiovascular diseases are a contributing factor to amyloid deposition, it would mean looking at amyloid-directed treatments, which does not follow the current trend to focus on targeting neurofibrillary tangles.

The link between ß-amyloid and cardiovascular disease is characterized in cerebral amyloid angiopathy (CAA), which is the deposition of ß-amyloid in blood vessels, a topic mentioned in my Week 3 post. Vascular deposits are known to have Aß40, which is much more soluble than Aß42 that is found in AD. And it is worth mentioning that capillary CAA, found in AD, which presented Aß42 deposits in the glia differed from arterial CAA which simply finds Aß40 deposits in arterial walls.

Cholesterol has long been a risk factor for AD and they play an important role in amyloid deposition. Sinohara et al. in 2014 find that cholesterol increases the activity of ß-secretase or γ-secretase which then increases the amount of ß-amyloid being produced. However, Zissimopoulos et al. in 2017’s study of cholesterol-lowering drugs, statins, found that they lower the risk for AD. It seems that statins can play a major role in limiting the emergence of AD when symptoms are barely present.

The following is taken from a study by Li, Lin, and Huang in 2018 and summarizes prior studies of Aß and statins:

There seem to be somewhat mixed results in the study of statins, but the evidence still seems promising. Treating AD with statins might be the new direction my research takes me in the final weeks of this Senior Project. Cholesterol buildup due to cardiovascular abnormalities may lead to a buildup of ß-amyloid in the brain that triggers the amyloid cascade. There is still quite a bit of research to be done on this topic and I hope to explore it in the weeks to come.

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