Molecular Pathogenesis of Alzheimer's Disease: An Update

Sanabria-Castro, Alfredo; Alvarado-Echeverría, Ileana; Monge-Bonilla, Cecilia

doi:10.1159/000464422

Cited by 336 publications

(266 citation statements)

References 103 publications

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“…In our study, NOR test results showed significant improvement in memory following both resistant and strength exercises in AD animals, which is in line with other similar studies [34, 35]. Based on the cholinergic hypothesis of AD, any reduction in the acetylcholine level is the probable cause of AD [36]. Also, the degeneration of cholinergic neurons in basal forebrain plays a key role in AD-induced memory loss and cognitive impairment [37].…”

Section: Discussionsupporting

confidence: 91%

Exercise Improves Recognition Memory and Acetylcholinesterase Activity in the Beta Amyloid-Induced Rat Model of Alzheimer’s Disease

et al. 2018

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Objective: A correlation between physical exercise and cognitive improvement has been found in Alzheimer’s disease (AD). This study aimed to investigate the effects of aerobic and resistance exercise on the recognition memory and acetylcholinesterase (AChE) activity in beta amyloid (Aβ) model of AD in rat. Materials and Methods: Fifty male 8-week-old Wistar rats (250–280 g) were divided into 5 groups (n = 10 each) of control, sham surgery, Aβ-received sedentary, Aβ-received with aerobic exercise and Aβ-received with resistance exercise. AD was induced by intracerebroventricular injection of Aβ_25–35 peptide. The sham surgery group received normal saline using the same route and condition. Two groups of Aβ-received animals were trained by treadmill for aerobic exercise and by ladder for strength exercise for 8 weeks (4 days/week). Novel object recognition (NOR) task was used to assess recognitional memory in groups. AChE activity in the brain tissue was assessed using the Spectrophotometry method. Results: There was no significant difference in memory index and AChE activity between the sham surgery and control groups (p > 0.05). Also, impairment of NOR indices was seen in the Aβ-injected sedentary rats (p < 0.05). However, both aerobic and strength training improved the exploration index in this test (p < 0.05). Further, AChE activity increased in the Aβ-injected sedentary group but declined in the aerobic and resistance exercise groups (p < 0.01). Conclusion: Aerobic and resistance exercise could improve recognition memory and decrease AChE activity in Aβ-induced AD in rats. The decrease in AChE activity may be one of the mechanisms by which exercise improves cognition and memory in AD.

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Section: Discussionsupporting

confidence: 91%

Exercise Improves Recognition Memory and Acetylcholinesterase Activity in the Beta Amyloid-Induced Rat Model of Alzheimer’s Disease

et al. 2018

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“…[1] They are found in AD brains and contain high levels of Cu 2 + and Zn 2 + ions embedded with aggregates of the amyloid-b (Ab)p eptide. [1] They are found in AD brains and contain high levels of Cu 2 + and Zn 2 + ions embedded with aggregates of the amyloid-b (Ab)p eptide.…”

Section: Introductionmentioning

confidence: 99%

Kinetics Are Crucial When Targeting Copper Ions to Fight Alzheimer's Disease: An Illustration with Azamacrocyclic Ligands

Conte-Daban

Beyler

Tripier

et al. 2018

Chemistry A European J

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Targeting copper ions to either remove or redistribute them is currently viewed as a possible therapeutic strategy in the context of Alzheimer's disease (AD). Thermodynamic parameters, as for instance the copper(II) affinity of the drug candidate or the copper(II) over zinc(II) selectivity, are considered in the design of the drug candidate. In contrast, kinetic factors have been overlooked despite their probable high importance. In the present article, we use a series of azamacrocyclic ligands to demonstrate that kinetic issues must be taken into account when designing copper‐targeting drug candidates in the context of AD.

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“…It reduces tau’s affinity for microtubules, and increases its likelihood to aggregate and fibrillize [309]. This leads to destabilization of microtubules with subsequent axonal transport failure and neurodegeneration, which can be offset or corrected by microtubule-stabilizing drugs [24, 40, 405].…”

Section: Tau Pathologymentioning

confidence: 99%

Current state of Alzheimer’s fluid biomarkers

et al. 2018

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

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Molecular Pathogenesis of Alzheimer's Disease: An Update

Cited by 336 publications

References 103 publications

Exercise Improves Recognition Memory and Acetylcholinesterase Activity in the Beta Amyloid-Induced Rat Model of Alzheimer’s Disease

Exercise Improves Recognition Memory and Acetylcholinesterase Activity in the Beta Amyloid-Induced Rat Model of Alzheimer’s Disease

Kinetics Are Crucial When Targeting Copper Ions to Fight Alzheimer's Disease: An Illustration with Azamacrocyclic Ligands

Current state of Alzheimer’s fluid biomarkers

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