Week 3: A Long Way to Go

Mar 24, 2020

Hey everyone! It seems every week my research seems to get tougher and tougher. Last week, I had found contradictory evidence about the role of hypoperfusion in AD. I decided that this week, I would look even deeper, into the science behind the connection between cerebral hypoperfusion and AD.

My first question was simple: How did those three studies (Love and Miners, Hansson et al., Austin et al.) find a connection between a cerebrovascular disease and AD in the first place? And the answer was pretty immediately found. I revisited the study conducted by Love and Miners which clearly detailed that there is a perfusion deficit in AD that may be a secondary cause of the accumulation of Aß. As I explained last week, they find that abnormalities that cause vasoconstriction dominate the early stages of AD. One of these abnormalities included cholinergic denervation. In a study conducted by Roher et al. in 2006, it was found that cholinergic deprivation is actually a cause of cerebral hypoperfusion and a “breached blood-brain-barrier (BBB).” It has also been found to lead to the deposition of Aß not in the brain (as is observed in AD) but in blood vessels. This was something I had actually discovered when doing my background research for my Senior Project and it was surprising to discover this theory once again.

As I began to look into cholinergic denervation I actually developed a new theory. I found a study by Wang, Zhang, and Tang (2009) that connected cholinergic denervation to VaD, something I thought I could ignore after Week 1. But the study actually found that cholinergic deficits, which are not fully understood, may be related to the cognitive impairments observed in VaD. I remembered that the symptoms of VaD almost mirrored that of AD. If it is cholinergic denervation that was leading to cognitive impairment as well as Aß deposits in blood vessels, I may have made a significant discovery in the role of cardiovascular abnormalities in the emergence of AD.

There is still tons to explore with cholinergic denervation, cerebral hypoperfusion, and the emergence of AD in future weeks. Although, I feel like I’ve made significant progress towards answering my research question.

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