Alzheimer's disease: The role of proteins in formation, mechanisms, and new therapeutic approaches

Gholami, Amirreza

doi:10.1016/j.neulet.2023.137532

Cited by 15 publications

(6 citation statements)

References 218 publications

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“…Each APOE isoform appears to be differentially associated with amyloid β (Aβ)-related and Aβ-independent pathways involved in the course of AD (e.g., neuroinflammation, vascular function, blood-brain barrier function, and so on), ultimately altering the net risk of incident AD [34]. Previous research has specifically shown the crucial role of APOE in the metabolism of Aβ [37][38][39][40]. Isoform-dependent binding to Aβ regulates its production and clearance.…”

Section: The Multifaceted Role Of Apolipoprotein E In the Brainmentioning

confidence: 99%

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review

Liampas,

Kyriakoulopoulou,

Siokas

et al. 2024

IJMS

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In this narrative review, we delved into the intricate interplay between Apolipoprotein E (APOE) alleles (typically associated with Alzheimer’s disease—AD) and alpha-synucleinopathies (aS-pathies), involving Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and multiple-system atrophy (MSA). First, in-vitro, animal, and human-based data on the exacerbating effect of APOE4 on LB pathology were summarized. We found robust evidence that APOE4 carriage constitutes a risk factor for PDD—APOE2, and APOE3 may not alter the risk of developing PDD. We confirmed that APOE4 copies confer an increased hazard towards DLB, as well. Again APOE2 and APOE3 appear unrelated to the risk of conversion. Of note, in individuals with DLB APOE4, carriage appears to be intermediately prevalent between AD and PDD-PD (AD > DLB > PDD > PD). Less consistency existed when it came to PD; APOE-PD associations tended to be markedly modified by ethnicity. Finally, we failed to establish an association between the APOE gene and MSA. Phenotypic associations (age of disease onset, survival, cognitive–neuropsychiatric- motor-, and sleep-related manifestations) between APOE alleles, and each of the aforementioned conditions were also outlined. Finally, a synopsis of literature gaps was provided followed by suggestions for future research.

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Section: The Multifaceted Role Of Apolipoprotein E In the Brainmentioning

confidence: 99%

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review

Liampas,

Kyriakoulopoulou,

Siokas

et al. 2024

IJMS

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“…According to the WHO, the number of people afflicted by AD will reach 66 million in 2030 and about 115 million by 2050. AD causes neuronal cell death, the development of neurofibrillary tangles composed of hyperphosphorylated tau protein and the formation of amyloid beta (Aβ) or senile plaques [14], as well as significant losses of cortically projecting cholinergic neurons and a reduction in the presynaptic markers of the cholinergic system. Low levels of acetylcholine in patients are associated with memory loss and a gradual learning decrease [15].…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Acetylcholinesterase Sensors for Anti-Alzheimer’s Disease Drug Determination

Ivanov,

Shamagsumova,

Larina

et al. 2024

Biosensors

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Neurodegenerative diseases and Alzheimer’s disease (AD), as one of the most common causes of dementia, result in progressive losses of cholinergic neurons and a reduction in the presynaptic markers of the cholinergic system. These consequences can be compensated by the inhibition of acetylcholinesterase (AChE) followed by a decrease in the rate of acetylcholine hydrolysis. For this reason, anticholinesterase drugs with reversible inhibition effects are applied for the administration of neurodegenerative diseases. Their overdosage, variation in efficiency and recommendation of an individual daily dose require simple and reliable measurement devices capable of the assessment of the drug concentration in biological fluids and medications. In this review, the performance of electrochemical biosensors utilizing immobilized cholinesterases is considered to show their advantages and drawbacks in the determination of anticholinesterase drugs. In addition, common drugs applied in treating neurodegenerative diseases are briefly characterized. The immobilization of enzymes, nature of the signal recorded and its dependence on the transducer modification are considered and the analytical characteristics of appropriate biosensors are summarized for donepezil, huperzine A, rivastigmine, eserine and galantamine as common anti-dementia drugs. Finally, the prospects for the application of AChE-based biosensors in clinical practice are discussed.

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“…Alzheimer's disease (AD) is the most common neurodegenerative disease, whose classical phenotype is prominent long-term memory deficits that progress into dementia. Pathophysiological hallmarks of AD include extracellular amyloid-beta (Aβ) plaques, intracellular neurofibrillary tau tangles, and neuroinflammation (Gholami 2023 ; Tzioras et al 2023 ). Currently, AD remains incurable; however, treatments are available that can alleviate symptoms and enhance the quality of life for those affected (Scheltens et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, AD remains incurable; however, treatments are available that can alleviate symptoms and enhance the quality of life for those affected (Scheltens et al 2021 ). The elucidation of cellular and molecular mechanisms contributing to AD pathogenesis is crucial for identifying new therapeutic targets (Gholami 2023 ). Mechanisms such as oxidative damage and systemic inflammation may accelerate the progression of AD (Chen and Zhong 2014 ; Bello-Corral et al 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice

Reyes-Reyes,

Brown,

Trial

et al. 2024

Exp Brain Res

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Apolipoprotein E ε4 allele (APOE4) is the predominant genetic risk factor for late-onset Alzheimer’s disease (AD). APOE4 mouse models have provided advances in the understanding of disease pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects like food and bedding can be major sources of changes in rodent microflora. Alterations in intestinal microbial ecology can cause mucosal barrier impairment and increase pro-inflammatory signals. The present study examined the role of sterile and non-sterile food and housing on redox indicators and the immune status of humanized-APOE4 knock-in mice (hAPOe4). hAPOE4 mice were housed under sterile conditions until 22 months of age, followed by the transfer of a cohort of mice to non-sterile housing for 2 months. At 24 months of age, the redox/immunologic status was evaluated by flow cytometry/ELISA. hAPOE4 females housed under non-sterile conditions exhibited: (1) higher neuronal and microglial oxygen radical production and (2) lower CD68+ microglia (brain) and CD8+ T cells (periphery) compared to sterile-housed mice. In contrast, hAPOE4 males in non-sterile housing exhibited: (1) higher MHCII+ microglia and CD11b+CD4+ T cells (brain) and (2) higher CD11b+CD4+ T cells and levels of lipopolysaccharide-binding protein and inflammatory cytokines in the periphery relative to sterile-housed mice. This study demonstrated that sterile vs. non-sterile housing conditions are associated with the activation of redox and immune responses in the brain and periphery in a sex-dependent manner. Therefore, housing status may contribute to variable outcomes in both the brain and periphery.

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Alzheimer's disease: The role of proteins in formation, mechanisms, and new therapeutic approaches

Cited by 15 publications

References 218 publications

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review

Apolipoprotein E Gene in α-Synucleinopathies: A Narrative Review

Electrochemical Acetylcholinesterase Sensors for Anti-Alzheimer’s Disease Drug Determination

Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice

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