Review of Alzheimer’s disease drugs and their relationship with neuron-glia interaction

Ajenikoko, Michael Kunle; Ajagbe, Abayomi Oyeyemi; Onigbinde, Oluwanisola Akanji; Okesina, Akeem Ayodeji; Tijani-Adekilekun, Ahmad

doi:10.1016/j.ibneur.2022.11.005

Cited by 23 publications

(11 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Activated astrocytes have been shown to distribute spatially similar to Aβ plaques in cortical regions of AD patients [ 42 , 43 ]. These astrocytes might penetrate Aβ plaques aiding in their separation from the surrounding neural fiber network and engulfing them [ 44 , 45 ]. Additionally, our findings unveiled a concomitant reduction in neurogenesis as the pathological grade of AD patients escalated, characterized by a significant decline in cells expressing DCX + and CR + Prox1 + cells, particularly in the ML, GCL, and SGZ regions.…”

Section: Discussionmentioning

confidence: 99%

Reduced neurogenesis in human hippocampus with Alzheimer's disease

Cao,

Liu,

Bian

et al. 2023

Brain Pathology

View full text Add to dashboard Cite

Adult hippocampal neurogenesis (AHN), essential for the plasticity of hippocampal structure and function, may be disrupted in Alzheimer‘s disease (AD). However, the relationship between the changes in AHN and AD‐related pathology in humans remains uncertain. By utilizing advanced immunostaining techniques, we could identify multiple biomarkers representing different stages of AHN in postmortem human hippocampal tissue that exhibited various AD‐related neuropathological changes. In this study, we observed a significant presence of neurogenic cells in the hippocampus's dentate gyrus (DG) region in 30 individuals, including 14 individuals diagnosed with AD‐related neuropathological changes and the remaining 16 individuals without any neurological diseases. Further investigation revealed that patients with AD exhibited pronounced astrogliosis and reduced neurogenesis. Specifically, the number of neuroblasts, immature and early mature granule cells decreased significantly as AD advanced. Although the number of neural stem cells (NSCs) remained unchanged in AD patients compared with mentally healthy individuals, they tended to be more quiescent state regulated by Notch and bone morphogenetic protein (BMP) signaling pathways. These abnormalities were strongly associated with the neuropathological alterations in AD patients. These research findings provide potential insights into the underlying mechanisms that underpin the pathogenesis of AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Reduced neurogenesis in human hippocampus with Alzheimer's disease

Cao,

Liu,

Bian

et al. 2023

Brain Pathology

View full text Add to dashboard Cite

show abstract

“…Neurons are the most basic structural and functional units in neural networks. They contain the protrusions and cytosol ( Ajenikoko et al, 2023 ). The cell body consists of the nucleus, the cell membrane and the cytoplasm, while the protrusions are divided into dendrites and axons.…”

Section: Methodsmentioning

confidence: 99%

The laws and effects of terahertz wave interactions with neurons

Gong

et al. 2023

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Introduction: Terahertz waves lie within the energy range of hydrogen bonding and van der Waals forces. They can couple directly with proteins to excite non-linear resonance effects in proteins, and thus affect the structure of neurons. However, it remains unclear which terahertz radiation protocols modulate the structure of neurons. Furthermore, guidelines and methods for selecting terahertz radiation parameters are lacking.Methods: In this study, the propagation and thermal effects of 0.3–3 THz wave interactions with neurons were modelled, and the field strength and temperature variations were used as evaluation criteria. On this basis, we experimentally investigated the effects of cumulative radiation from terahertz waves on neuron structure. Results: The results show that the frequency and power of terahertz waves are the main factors influencing field strength and temperature in neurons, and that there is a positive correlation between them. Appropriate reductions in radiation power can mitigate the rise in temperature in the neurons, and can also be used in the form of pulsed waves, limiting the duration of a single radiation to the millisecond level. Short bursts of cumulative radiation can also be used. Broadband trace terahertz (0.1–2 THz, maximum radiated power 100 μW) with short duration cumulative radiation (3 min/day, 3 days) does not cause neuronal death. This radiation protocol can also promote the growth of neuronal cytosomes and protrusions.Discussion: This paper provides guidelines and methods for terahertz radiation parameter selection in the study of terahertz neurobiological effects. Additionally, it verifies that the short-duration cumulative radiation can modulate the structure of neurons.

show abstract

“…Donepezil has a relatively high systemic bioavailability of 86.8% and takes 3–4 h to reach peak plasma concentrations. [ 21 ] It has a t 1/2 of 70 h, making it suitable for once-daily dosing. [ 22 ] Studies have found 5 mg and 10 mg once-daily doses to be effective in reducing tau-protein expression, decreasing hippocampal atrophy, lowering serum Aβ levels, and improving cognitive performance in patients of AD.…”

Section: Symptom-mitigating Drugsmentioning

confidence: 99%

Guidelines for pharmacotherapy in Alzheimer’s disease – A primer on FDA-approved drugs

Varadharajan,

Davis,

Ghosh

et al. 2023

JNRP

View full text Add to dashboard Cite

The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, to improve the quality of life of patients and caregivers. Alzheimer’s disease (AD), a neurodegenerative disease, is the most common form of amnestic dementia in the geriatric population. Pathophysiology of AD is widely attributed to aggregation of amyloid-beta (Aβ) plaques and hyperphosphorylation of tau proteins. Initial treatment modalities aimed to increase brain perfusion in a non-specific manner. Subsequent therapy focused on rectifying neurotransmitter imbalance in the brain. Newer drugs modify the progression of the disease by acting against aggregated Aβ plaques. However, not all drugs used in therapy of AD have been granted approval by the United States Food and Drug Administration (FDA). This review categorizes and summarizes the FDA-approved drugs in the treatment of AD in a manner that would make it a convenient reference for researchers and practicing physicians alike. Drugs that mitigate symptoms of dementia may be categorized into mitigators of Behavioral and Psychological Symptoms of Dementia (BPSD), and mitigators of cognitive decline. BPSD mitigators include brexpiprazole, an atypical antipsychotic with a once-daily dosage suited to treat agitation in dementia patients, and suvorexant, an orexin receptor antagonist used to treat sleep disturbances. Cognitive decline mitigators include cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine and glutamate inhibitors such as memantine. Donepezil is the most commonly prescribed drug. It is cheap, well-tolerated, and may be prescribed orally once daily, or as a transdermal patch once weekly. It increases ACh levels, enhances oligodendrocyte differentiation and also protects against Aβ toxicity. However, regular cardiac monitoring is required due to reports of cardiac conduction side effects. Rivastigmine requires a twice-daily oral dosage or once-daily replacement of transdermal patch. It has fewer cardiac side effects than donepezil, but local application-site reactions have been noted. Galantamine, in addition to improving cognitive symptoms in a short span of time, also delays the development of BPSDs and has minimal drug-drug interactions by virtue of having multiple metabolic pathways. However, cardiac conduction disturbances must be closely monitored for. Memantine, a glutamate regulator, acts as an anti-Parkinsonian agent and an antidepressant, in addition to improving cognition and neuroprotection, and requires a once-daily dosage in the form of immediate-release or sustained-release oral tablets. Disease-modifying drugs such as aducanumab and lecanemab reduce the Aβ burden. Both act by binding with fibrillary conformations of Aβ plaques in the brain. These drugs have a risk of causing amyloid-related imaging abnormalities, especially in persons with ApoE4 gene. Aducanumab is administered once every 4 weeks and lecanemab once every 2 weeks. The decision on the choice of the drug must be made after considering the availability of drug, compliance of patient (once-daily vs. multiple doses daily), cost, specific comorbidities, and the risk-benefit ratio for the particular patient. Other non-pharmacological treatment modalities must also be adopted to have a holistic approach toward the treatment of AD.

show abstract

Review of Alzheimer’s disease drugs and their relationship with neuron-glia interaction

Cited by 23 publications

References 111 publications

Reduced neurogenesis in human hippocampus with Alzheimer's disease

Reduced neurogenesis in human hippocampus with Alzheimer's disease

The laws and effects of terahertz wave interactions with neurons

Guidelines for pharmacotherapy in Alzheimer’s disease – A primer on FDA-approved drugs

Contact Info

Product

Resources

About