Long Term Consequences of Brain Ischemia in the Development of Alzheimer's Disease

Transient ischemia is the loss of blood supply to tissue followed by its restoration, leading to cell death, tissue damage, and harmful cell signaling. While the paper here is focused on connecting the significant ischemia of stroke with the later development of Alzheimer's disease, it is also the case that aging brains undergo many unnoticed, tiny ischemic events over the years. These minuscule strokes have the same root cause as large, evident strokes, meaning the rupture or blockage of a blood vessel in the brain, but much smaller vessels and surrounding volumes of tissue are involved. That damage likely adds up over time, however, contributing to the onset and progression of neurodegenerative conditions such as Alzheimer's disease.

New clinical and experimental studies indicate epidemiological and neuropathological links connecting ischemic brain neurodegeneration with the genotype and phenotype of Alzheimer's disease. Human investigations have revealed that Alzheimer's disease is a risk factor for stroke and vice versa, indicating that the same or closely related pathological mechanisms may be involved in the development of both disorders. Animal studies have also presented a synergistic link between brain ischemia and Alzheimer's disease, leading to an increased risk of cognitive decline and development of Alzheimer's disease-type dementia.

The main cause of ischemic stroke in humans is atherosclerosis. Atherosclerosis is also associated with Alzheimer's disease. At least 33% cases of Alzheimer's disease have neuropathological changes resulting from small vessel arteriosclerosis. Atherosclerosis has been found to coexist with cerebral amyloid angiopathy and it also correlates well with cognitive decline. On the other hand, the increased level of amyloid in the post-ischemic brain causes the accumulation of amyloid not only in the brain tissue, but also in the vessel wall, causing the development of cerebral amyloid angiopathy.

Reduction in the length of cerebral vessels post-ischemia or impaired cerebral blood flow in the brain as a result of vasoconstriction and/or the development of cerebral amyloid angiopathy not only limits the transport of energy substrates and the supply of oxygen and nutrients to the brain through the blood-brain barrier after ischemia, but also reduces the clearance of potential neurotoxins from the brain, such as amyloid. This leads to the idea that brain vascular diseases, such as ischemic brain episode, may make the regions in the brain more susceptible to Alzheimer's disease pathology, due to impaired clearance of amyloid from the brain and dysfunctional tau protein. Alternatively, post-ischemic brain neurodegeneration and Alzheimer's disease may finally represent independent but convergent common pathological mechanisms, and can therefore be expected to have common proteomic and genomic risk factors.

Link: https://doi.org/10.3389/fnagi.2021.636653

Comments

"it is also the case that aging brains undergo many unnoticed, tiny ischemic events over the years. These minuscule strokes have the same root cause as large, evident strokes, meaning the rupture or blockage of a blood vessel in the brain, but much smaller vessels and surrounding volumes of tissue are involved. That damage likely adds up over time,"

Thats what scares me most and maybe it will be the most difficult part to do anything about? Both in terms of prevention and treatments.

Posted by: thomas.a at April 2nd, 2021 6:43 AM

@thomas.a:
It depends on what its cause is. If it's due to, say, blood vessel stiffening, then a glucosepane breaker or an anticalcification treatment could prevent it. If it's due to amyloid plaques around the vessels, then antiamyloid treatments could address it. We'll see in the next years.

Posted by: Antonio at April 2nd, 2021 7:17 AM

@Antonio: I hope you are correct. I fear that the damages small blood cloths creates are too small to spend resources on repairing. That it could be done but getting that 100% efficiency is so costly to society it wouldn't be done. Its a bit difficult to explain.

Posted by: thomas.a at April 2nd, 2021 7:56 AM

@thomas.a
The micro damage is more amenable to natural repair. Small blood vessels form all the time so, if the kids is blood supply is gradual there body will create backup vessels. Also, the brain might repair port compensate for some if the neural damage. However, worrying about micro damage is of lower priority against stroke and heart attacks.

Posted by: Cuberat at April 2nd, 2021 8:50 PM

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