Week 5: Taking a Few More Steps Back

Apr 18, 2020

Hey everyone! In my last post, I did a bit of exploration into amyloid-directed treatments as well as looked at the bigger picture of the pathology of Alzheimer’s disease. I’d like to reiterate that the hope is to get a better understanding of the role the cardiovascular system plays in what is largely assumed to be only a neurological disorder. And while that very well may be the case, it is clear from the first few weeks of research that blood perfusion could be a possible connection to the deposition of amyloid plaques. In fact, cholesterol-lowering drugs were found to lower the risk of AD by targeting other forms of amyloid, such as the types being deposited in blood vessels.

But this week, I wanted to continue this exploration by looking at the ways current research has targeted the neurofibrillary tangles. Tauists, as they are known, argue that targeting neurofibrillary tangles may prove more effective than amyloid-directed treatments.

While tau is a protein that traditionally stabilizes microtubules in charge of the transport of nutrients and precursors of neurotransmitters, when they are hyperphosphorylated, this transport is disrupted. When the tau dissociates, the microtubule loses stability, resulting in neuronal dysfunction. Although the amyloid cascade hypothesis argues that it is the senile plaques that eventually lead to degeneration, there is other evidence showing that these tangles directly cause cell death. One such example is FDP-17, a form of dementia where the hyperphosphorylated tau itself causes neuronal death.

Several drugs are currently being tested to assess whether it is possible to intervene and prevent tau aggregation and the formation of tangles. The shift to tangle-directed treatments is a fairly recent development in the world of neuroscience, and thus, there have not been concrete results as to the effectiveness of such treatments. TauRx and tau active vaccines are two possible treatments that are currently ongoing clinical trials.

As a result of realizing that ß-amyloid accumulates well before the onset of AD as well as the general acceptance of the amyloid cascade hypothesis, research into AD treatments largely concern preventing the disease even before cognitive impairments begin to appear. What seems to be more difficult is treating AD once cognitive decline is already present.


Since these tau-targeted treatments are newer, there seems to be limited information on the success of this approach. However, all of this research over the past 2 weeks has definitely given me a broader perspective for how to approach my research question in the coming weeks. The current lockdown has  given me lots of time to think about my research question and getting a better understanding of the disease I have been exploring has kindled a fire within my project and excites me for what I will research in the weeks ahead.

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