Ischemia as a common trigger for Alzheimer’s disease

Elman-Shina, Karin; Efrati, Shai

doi:10.3389/fnagi.2022.1012779

Cited by 22 publications

(30 citation statements)

References 55 publications

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“…The disease-specific hyperglycemia and insulin resistance could initiate signaling pathways that impair neuronal glucose metabolism and thus stimulate phosphorylation and cleavage of tau as a cornerstone of tau accumulation and tau-mediated neurodegeneration [ 42 , 43 ]. Furthermore, the accumulation of tau and β-amyloid in AD can be accelerated in the context of cardio- and cerebrovascular diseases [ 44 , 45 ]. Due to a reduced cerebral blood flow and resulting hypoxia-induced ischemia, cerebrovascular diseases can induce a dysfunction of blood–brain barrier and mitochondria, enabling the deposition of misfolded proteins [ 44 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the accumulation of tau and β-amyloid in AD can be accelerated in the context of cardio- and cerebrovascular diseases [ 44 , 45 ]. Due to a reduced cerebral blood flow and resulting hypoxia-induced ischemia, cerebrovascular diseases can induce a dysfunction of blood–brain barrier and mitochondria, enabling the deposition of misfolded proteins [ 44 , 46 ]. On the other hand, cerebrovascular diseases and tau pathology appear to have a reverse association [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

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The comorbidity and co-medication profile of patients with progressive supranuclear palsy

Greten,

Wegner,

Jensen

et al. 2023

J Neurol

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Background Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. Objectives To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. Methods Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug–drug interactions were evaluated using AiDKlinik®. Results In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug–drug interactions was higher in PSP patients, especially severe and moderate interactions. Conclusions PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The comorbidity and co-medication profile of patients with progressive supranuclear palsy

Greten,

Wegner,

Jensen

et al. 2023

J Neurol

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“…If the trend in ischemic brain injury continues, by 2030 approximately 12 million cases will die, 70 million will survive ischemia, and each year there will be disability for over 200 million years [ 4 , 6 ]. Based on the latest clinical and experimental evidence, it was hypothesized that an episode of brain ischemia may contribute to the development of Alzheimer’s disease [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Growing evidence shows that brain ischemia causes neurodegeneration of the Alzheimer’s disease-like phenotype and genotype, and provides new insight into the similar mechanisms of changes that may be involved in the development of both diseases, but the ultimate answer underlying their co-development remains unknown [ 17 , 18 , 21 ].…”

Section: Brain Ischemiamentioning

confidence: 99%

Trans- and Cis-Phosphorylated Tau Protein: New Pieces of the Puzzle in the Development of Neurofibrillary Tangles in Post-Ischemic Brain Neurodegeneration of the Alzheimer’s Disease-like Type

Pluta,

Czuczwar

2024

IJMS

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Recent evidence indicates that experimental brain ischemia leads to dementia with an Alzheimer’s disease-like type phenotype and genotype. Based on the above evidence, it was hypothesized that brain ischemia may contribute to the development of Alzheimer’s disease. Brain ischemia and Alzheimer’s disease are two diseases characterized by similar changes in the hippocampus that are closely related to memory impairment. Following brain ischemia in animals and humans, the presence of amyloid plaques in the extracellular space and intracellular neurofibrillary tangles was revealed. The phenomenon of tau protein hyperphosphorylation is a similar pathological feature of both post-ischemic brain injury and Alzheimer’s disease. In Alzheimer’s disease, the phosphorylated Thr231 motif in tau protein has two distinct trans and cis conformations and is the primary site of tau protein phosphorylation in the pre-entanglement cascade and acts as an early precursor of tau protein neuropathology in the form of neurofibrillary tangles. Based on the latest publication, we present a similar mechanism of the formation of neurofibrillary tangles after brain ischemia as in Alzheimer’s disease, established on trans- and cis-phosphorylation of tau protein, which ultimately influences the development of tauopathy.

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“…It also seems possible that a link between cerebral ischemia, chaperones, and extracellular vesicles may exist. It is well known that brain ischemia (due to several reasons such as cardiac arrest, shock, carotid occlusion, hypotension, asphyxia, or anemia) may contribute to the development of Alzheimer’s disease [ 255 ]. On the other hand, it was shown that the exosomes of neurons act as an endogenous post-ischemic protective factor by inhibiting microglial phagocytosis and thus mitigating ischemia-induced neuronal death [ 256 ].…”

Section: Therapeutic Applications Of Evs and Molecular Chaperones In ...mentioning

confidence: 99%

Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS

Noori

Filip

Nazmara

et al. 2023

IJMS

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Many neurodegenerative disorders are characterized by the abnormal aggregation of misfolded proteins that form amyloid deposits which possess prion-like behavior such as self-replication, intercellular transmission, and consequent induction of native forms of the same protein in surrounding cells. The distribution of the accumulated proteins and their correlated toxicity seem to be involved in the progression of nervous system degeneration. Molecular chaperones are known to maintain proteostasis, contribute to protein refolding to protect their function, and eliminate fatally misfolded proteins, prohibiting harmful effects. However, chaperone network efficiency declines during aging, prompting the onset and the development of neurological disorders. Extracellular vesicles (EVs) are tiny membranous structures produced by a wide range of cells under physiological and pathological conditions, suggesting their significant role in fundamental processes particularly in cellular communication. They modulate the behavior of nearby and distant cells through their biological cargo. In the pathological context, EVs transport disease-causing entities, including prions, α-syn, and tau, helping to spread damage to non-affected areas and accelerating the progression of neurodegeneration. However, EVs are considered effective for delivering therapeutic factors to the nervous system, since they are capable of crossing the blood–brain barrier (BBB) and are involved in the transportation of a variety of cellular entities. Here, we review the neurodegeneration process caused mainly by the inefficiency of chaperone systems as well as EV performance in neuropathies, their potential as diagnostic biomarkers and a promising EV-based therapeutic approach.

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Ischemia as a common trigger for Alzheimer’s disease

Cited by 22 publications

References 55 publications

The comorbidity and co-medication profile of patients with progressive supranuclear palsy

The comorbidity and co-medication profile of patients with progressive supranuclear palsy

Trans- and Cis-Phosphorylated Tau Protein: New Pieces of the Puzzle in the Development of Neurofibrillary Tangles in Post-Ischemic Brain Neurodegeneration of the Alzheimer’s Disease-like Type

Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS

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