Brain Ischemia as a Prelude to Alzheimer's Disease.

Ryszard Pluta,Sławomir Januszewski,Stanisław J Czuczwar

doi:10.3389/fnagi.2021.636653

Ryszard Pluta, Sławomir Januszewski + Show 1 more

Open Access

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

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Abstract

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.

Highlights

Brain ischemia and Alzheimer’s disease create a huge burden to the healthcare system and caregivers due to the lack of causal treatment
This review presents the phenotype and genotype of Alzheimer’s disease in post-ischemic brain neurodegeneration, such as neuropathology, amyloid, dysfunctional tau protein, and their genes, which altogether play an important role in the development of full-blown dementia (Figure 1)
The evidence demonstrates that post-ischemic brain damage causes the death of neuronal cells in the hippocampus and temporal cortex in a manner that is dependent on the amyloid and dysfunctional tau protein

Summary

INTRODUCTION

Brain ischemia and Alzheimer’s disease create a huge burden to the healthcare system and caregivers due to the lack of causal treatment. The amyloid is a neurotoxic substance that induces intracellular processes in post-ischemic neurons, astrocytes, and microglia, which further causes extra neurons and neuroglia injury and/or death following ischemia (Giulian et al, 1995; Pluta et al, 2012a) After ischemia, both diffuse and senile amyloid plaques in the hippocampus and cortex were observed in the human brain (Jendroska et al, 1995, 1997; Wisniewski and Maslinska, 1996; Qi et al, 2007). Genes: APP, amyloid protein precursor; BACE1, β-secretase; PSEN1, presenilin 1; PSEN2, presenilin 2; MAPT, Tau protein

Survival PPP

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CONCLUSION