Analyzing Different Hypotheses for Alzheimer’s Disease

There are many existing hypotheses for the pathogenesis for Alzheimer’s disease (AD), but none are fully verified. The most widely accepted hypothesis is the amyloid-beta hypothesis, which is partially due to the fact that it has been around for relatively long time. The foundation for this hypothesis is the fact that AB tangles have been found in the brains of patients with AD. Therefore, many have come to the conclusion that AB tangles prevent healthy cell function and trigger inflammation in the brain. Despite the plethora of research supporting the AB hypothesis, there have been little to no advancements in the treatments and therapies for AD. Another hypothesis for AD that opposes the AB hypothesis is the presenilin hypothesis. The presenilin hypothesis claims that AD is not caused by the production of AB peptides, but rather stalled ES complexes, which limits the amount of cuts y-secretase makes on APP substrate. This hypothesis proved that AB is merely a byproduct of AD. Lastly, researchers have also looked into how insulin resistance affects AD-related processes in the brain, and have gathered substantial evidence for the insulin resistance hypothesis. The link between Tau protein tangles and insulin resistance has been uncovered, suggesting the relevance of insulin in cognition and neurosynaptic health. Additionally, researchers found that insulin can trigger the non-amyloidogenic pathway, that is, the pathway that does not produce harmful AB peptides. In this review, I will criticize the limitation of each hypothesis, and finally select the most valid one.