Brain Ischemia as a Prelude to Alzheimer's Disease

We've known about this for years, 15 YEARS TO BE EXACT. What the fuck are YOU DOING to prevent this from happening? NOTHING? Good to know you're joining all the other incompetent persons in stroke.

Effect of a clinical stroke on the risk of dementia in a prospective cohort

 October 23, 2006

The latest useless shit here:

Brain Ischemia as a Prelude to Alzheimer's Disease

Ryszard Pluta^1*, Sławomir Januszewski¹ and Stanisław J. Czuczwar²

• ¹Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
• ²Department of Pathophysiology, Medical University of Lublin, Lublin, Poland

Transient ischemic brain injury causes massive neuronal death in the hippocampus of both humans and animals. This was accompanied by progressive atrophy of the hippocampus, brain cortex, and white matter lesions. Furthermore, it has been noted that neurodegenerative processes after an episode of ischemia-reperfusion in the brain can continue well-beyond the acute stage. Rarefaction of white matter was significantly increased in animals at 2 years following ischemia. Some rats that survived 2 years after ischemia developed severe brain atrophy with dementia. The profile of post-ischemic brain neurodegeneration shares a commonality with neurodegeneration in Alzheimer's disease. Furthermore, post-ischemic brain injury is associated with the deposition of folding proteins, such as amyloid and tau protein, in the intracellular and extracellular space. Recent studies on post-ischemic brain neurodegeneration have revealed the dysregulation of Alzheimer's disease-associated genes such as amyloid protein precursor, α-secretase, β-secretase, presenilin 1, presenilin 2, and tau protein. The latest data demonstrate that Alzheimer's disease-related proteins and their genes play a key role in the development of post-ischemic brain neurodegeneration with full-blown dementia in disease types such as Alzheimer's. Ongoing interest in the study of brain ischemia has provided evidence showing that ischemia may be involved in the development of the genotype and phenotype of Alzheimer's disease, suggesting that brain ischemia can be considered as a useful model for understanding the mechanisms responsible for the initiation of Alzheimer's disease.

Introduction

Presently, brain ischemia and Alzheimer's disease create a huge burden to the healthcare system and caregivers due to the lack of causal treatment. Both the diseases are the main causes of irreversible disability and dementia worldwide (Ballard et al., 2011; Pluta et al., 2011, 2020b,c,d; Kim and Lee, 2018; Lo et al., 2019), and there is a risk of stroke or Alzheimer's disease is one in three persons (Seshadri and Wolf, 2007). With increasing numbers of aging in the world, the number of subjects with dementia is forecast to reach 82 million by 2030 and 152 million by 2050 (Ballard et al., 2011). There are no causal treatments that could stop the development of dementia in both patients after stroke and Alzheimer's disease(WHY NOT?). For this reason, there is a lot of pressure to increase the understanding of the mechanisms of post-ischemic brain neurodegeneration in connection with its recommended relationship with Alzheimer's disease (Pluta, 2007b, 2019; Pluta et al., 2011, 2013a,b; Salminen et al., 2017) and to make causal therapy available (Ułamek-Kozioł et al., 2020a). It is noteworthy that more and more 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 (Chi et al., 2013; Tolppanen et al., 2013) and vice versa (Gamaldo et al., 2006), 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 (De la Tremblaye and Plamondon, 2011; Kiryk et al., 2011; Li et al., 2011; Cohan et al., 2015; Traylor et al., 2016; Salminen et al., 2017). The main cause of ischemic stroke in humans is atherosclerosis (Roher et al., 2004; Beach et al., 2007). Atherosclerosis is also associated with Alzheimer's disease (Farkas and Luiten, 2001; Thal et al., 2003; Beach et al., 2007). At least 33% cases of Alzheimer's disease have neuropathological changes resulting from small vessel arteriosclerosis (Kalaria, 2002). Atherosclerosis has been found to coexist with cerebral amyloid angiopathy and it also correlates well with cognitive decline (Thal et al., 2003; Pluta et al., 2009). 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 (Pluta et al., 2009; Hecht et al., 2018). Reduction in the length of cerebral vessels post-ischemia or impaired cerebral blood flow in the brain as a result of vasoconstriction (Wisniewski et al., 1995) and/or the development of cerebral amyloid angiopathy (Pluta et al., 2009; Hecht et al., 2018) 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 (Hecht et al., 2018). 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 (Farkas and Luiten, 2001) 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 (Traylor et al., 2016; Pluta et al., 2019a,b; Ułamek-Kozioł et al., 2020b).