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PooDendalNerveBlock t1_iu6ank1 wrote

The presence of neurofibrillary tangles and beta amyloid plaques (which recently have sparked controversy). Lead to the degradation of the cortex of the brain. Dementia is the term used to describe impaired cognitive status. The severity of the disease is typically generally attributed to the amount of neurofibrillary tangles. A decrease in the neurotransmitter acetylcholine is present as well. Drugs that increase this neurotransmitter help with symptomatic management but do not slow the profession of the disease.


twan_john t1_iu7uqjv wrote

There's some new research that looked into how sleep protects against Alzheimer's. "A study published in the journal Science revealed that cerebrospinal fluid carries these waste products away from the brain during deep sleep, acting as a guard to cognitive function . . . There’s also mounting research to suggest that getting too little—or even too much—sleep could increase your risk for Alzheimer’s disease."



doomedtobeme t1_iu86ylo wrote

I was taught something similar in uni maybe 3 years ago, sleep and quality of sleep is huuuuge. It's been found that in people with lack of sleep, that there's an abnormally high level of specific plaques and more related to dementia etc.

Shift workers are getting funked over big time, can't imagine how bad 30 years of those shifts are on the brain.


mazurzapt t1_iu9pxdd wrote

I read about these cerebrospinal fluids some years ago and I visualize that now when I go to sleep. Ok time for my brain to have a bath! Lol


griphookk t1_iu7uqf2 wrote

Speaking of acetylcholine- anticholinergic drugs (such as tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics) are significantly linked to early-onset dementia.

Taking an anticholinergic for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.

And, speaking of antihistamines- Benadryl. It’s criminal that it’s marketed for sleep and as “safe and non habit-forming”. It should NOT be taken regularly such as nightly for sleep, it is NOT safe and it IS habit forming/addictive. It’s so bad for you that in recreational drug communities it’s one of the number one things people tell others to stay away from.


PooDendalNerveBlock t1_iu9fhjz wrote

Thank you for the addition, this is something that should be brought in the spotlight. Appreciated.


geekbot2000 t1_iu7glvn wrote

I think the controversy you mentioned has to do with the causative nature of the amyloid plaques. Decades of research/therapeutics targeting the plaques have not produced improved clinical outcomes, the current thinking is that the plaques are a consequence of whatever else is causing alzie.


uiucengineer t1_iu7ibby wrote

You haven't heard: the study that originally showed the correlation is allegedly a fraud.


packpride85 t1_iu8dzlq wrote

That’s not the general consensus among researchers as that was a very specific scenario.


eddiepaperhands t1_iu93kau wrote

There’s also recent research suggesting that the cause is lower levels of soluble amyloid-beta and that the plaques - like Alzheimer’s - are a result of that.


CrateDane t1_iudcm3b wrote

No, that's not about the overall correlation - it's well established that Alzheimer's is correlated with amyloid plaques. The question is whether the amyloid plaques are causing the Alzheimer's. That likely fraudulent study showed that expressing this particular form of amyloid-beta in mouse brains led to Alzheimer-like symptoms alongside accumulation of a particular fragment. That was proposed to be an early precursor to the more severe plaques seen later on (or postmortem).


JPK12794 t1_iu8i33j wrote

There's a mutation in an enzyme that cleaves a protein called amyloid beta, amyloid beta is necessary for the brain and a part of normal physiological function when investigated in KO mice. In AD the protein starts cleaving AB into a toxic form AB42, as the ratio of this to healthy AB begins to shift aggregates build. Many things happen from here, you get resident immune cells trying to dispose of these building aggregates which can make things worse if they're not cleared via the CSF. Eventually this build up can cause problems with the neurovascular unit and the blood brain barrier meaning cells aren't supplied correctly and you see increases in for the sake of simplicity what I'll call toxins. These again cause cell death, this further contributes to toxic build up you start to get inflammatory responses which again make things worse and this cascade just keeps going. I've just finished my PhD thesis on brain inflammation at the BBB. There's still a huge amount we don't know but when I was growing 3D human cortical spheroids and staining them we did see breakdown of the synapses in particular when AD models were compared to controls. There's a lot left to learn about AD and many mechanisms just aren't fully understood.


dirtdueler t1_iu8tf1d wrote

Not on a physiological level but, in my cadaver lab at college one of the cadavers had Alzheimer’s. Their brain, unlike a normal one that is all wavy and bumpy and has that texture everyone associates with a brain, was very smooth and lacked definitive texture.


TopSpin247 t1_iu7xtb8 wrote

According to a 2013 study Oxysterols in the pathogenesis of major chronic diseases, hypercholesterolemia (specifically oxidized cholesterol) is a primary risk factor for Alzheimer's disease.

Oxidized cholesterol can penetrate the blood brain barrier, allowing long - term accumulation within the brain. This process is enhanced by an oxidative imbalance in the body (lack of antioxidants).

According to a 2012 study, plaque build up in the brain is a larger indicator of Alzheimer's progression than the APOE gene, often associated with the disease. It's just that testing for genotypes is easier than plaque imaging.

Brain autopsies in Alzheimer's patients show significantly more plaque build up in age-controlled brains vs controls. This study "strongly suggest that atherosclerosis-induced brain hypoperfusion (lack of blood flow) contributes to the clinical and pathological manifestations of AD."


darthjeff2 t1_iu8upkj wrote

Just another thing to add, we don't really have reliable ways to tell if someone is going to get or is currently developing Alzheimer's until symptoms set in- which makes it difficult to study. Further, most data we can get from human patients is gathered after they die (though I believe there are several long-term clinical trials that are begining to collect patient data during the development of the disease).

So the issue becomes developing models to study the disease (often in mice and cells cultured on plates). Turns out there's lots of ways to cause a mouse to have neuron degeneration, and not all of them are precisely what causes Alzheimer's disease. As a result, giving an exact and certain answer to this question isn't really possible (if it was we would be a lot closer to treating the disease).

For the most part, characteristics of the disease involves build up of misformed proteins in the brain. Some form outside of neurons (so called amyloid beta plaques) and some form within neurons themselves (amyloid fibrilary tangles). In most cases, the build up of proteins themselves does not seem to cause disease, but it may be a necessary step in some (not all) disease cases. So a lot of research is focused around how the body deals with misfolded proteins (which is related to some forms of cholesterol management, the blood-brain-barrier, waste removal, etc.) and how these proteins are misfolded in the first place.

Unfortunately, the nervous system is really complicated system, and there will likely never be a single answer to what causes this disease. It's similar to asking why a car breaks down- anything within the complicated system of a car can cause it to stop working. Sometimes it's an empty fuel tank, sometimes it's a loose cable. Often the breakdown of a car is accompanied with loud knocking or ticking noises from the engine- so it's important to study and understand the cause and effect of the knocking sound- but it's not the only reason a car stops working. Similar to Alzheimer's disease, amyloid plaques and Tau tangles are often associated with Alzheimer's (and we should ABSOLUTELY study the cause and affect of them) but (in my opinion) it's going to take a lot of dedicated work to understanding more about the nervous system as a whole to say for sure what's going on in any given case of Alzheimer's disease.


RegularBasicStranger t1_iu9c52l wrote

Some forms of Alzheimer's kill brain cells via choking blood capillaries so there is no blood circulation and no oxygen and toxin buildup (the blood capillaries may still be present, but no blood circulation so the blood is stale).

Some other forms form dried blood plaques to prevent neurotransmitters from reaching their intended neurons so signals terminate prematurely (dried blood plaques probably can be considered as a form of toxin buildup so blood capillaries getting choked is probably a reason).

So people who do not exercise enough probably will get Alzheimer (though old people exercising will put them at risk of stroke so old people getting Alzheimer is expected, but exercises like taichi and yoga probably can be done by old people to keep off Alzheimer's).