In our last article we took a macroscale look at Alzheimer’s Disease (AD). As we previously mentioned, there are many different hypotheses as to why AD occurs. In this article, let’s look at AD on a more microscale to examine the different possible explanations for Alzheimer’s Disease.
Beta-Amyloid Hypothesis
- A commonly found physical hallmark of AD is the presence of amyloid-beta plaques in aggregations throughout the brain
- This hypothesis suggests that these aggregates lead to a series of events ending in neurodegeneration
- There is evidence against this hypothesis. There are many cases of individuals with large deposits of amyloid plaques that do not show any signs of cognitive decline. Additionally, the amount of amyloid plaques in a patient with AD is not a good predictor of severity. Most notably, clinical trials for drugs that disrupt or remove the amyloid plaques does NOT prevent/slow the onset or progression of the disease (Makin, 2018)
Tau Hypothesis
- In addition to the amyloid plaques found in AD, scientists have found tau proteins that aggregate into neurofibrillary tangles (NFT), in the brains of individuals with AD.
- Under normal circumstances, tau proteins are important for stability of certain protein structures, however in AD, the aggregation of these proteins is thought to lead to neurotoxicity
- Additionally, the dysfunction of the tau proteins in AD is thought to contribute to disruption of the proteins they stabilize. This is seen as an additional factor that could contribute to the death of neurons in the brain (Mohandas, 2009).
- Additional research has provided conflicting data. Some studies have found evidence suggesting that tau buildups may provide some protection against neurodegeneration, while other studies have found data that suggests tau is purely pathological (Ding & Johnson, 2009).
Inflammation Hypothesis
- Studies of post-mortem (already dead) brain slices of individuals who had AD show significant levels of neuroimmune system inflammation
- Microglia, the immune cells of the nervous system, lead to the immune response and are thought to be activated by the presence of amyloid plaques and neurofibrillary tangles. It is suggested that in response the buildup of these proteins microglia launch an immune response that contributes to neurodegeneration (Kinney et al., 2018; Mohandas et al., 2009).
Vascular Hypothesis
- Data has consistently shown that vascular systems (blood carrying system) degrades with age and that treating vascular disease helps slow AD development
- It has been suggested that the breakdown in the vasculature may lead to leakage of blood proteins and pathogens into the nervous system.
- This release puts stress on the nervous system and, in turn, leads to the death of nervous tissue (Mohandas et al., 2009; Scheffer et al., 2021).
As you can see there are a lot of potential theories as to how AD occurs and progresses. These are only the 4 most talked about, but there are many other ones out there. I know we say this a lot, but everyday researchers are hard at work, trying to better understand AD. While there may not be great treatment options now, who knows what the future may hold! That being said, prevention is key! This is why it is so important to maintain a healthy lifestyle as a means of protecting our brains!
