• Biomolecules & Therapeutics
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• 제28권2호
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• pp.131-136
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• 2020

Hippocampal synaptic dysfunction is a hallmark of Alzheimer's disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.

• 생물정신의학
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• 제30권1호
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• pp.24-30
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• 2023

Objectives Alzheimer's disease (AD) is the most common form of dementia in older adults, damaging the brain and resulting in impaired memory, thinking, and behavior. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. The aim of our study was to identify differentially expressed genes associated with AD and combined biomarkers among them to improve AD risk prediction accuracy. Methods Machine learning methods were used to compare the performance of the identified combined biomarkers. In this study, three publicly available gene expression datasets from the hippocampal brain region were used. Results We detected 31 significant common genes from two different microarray datasets using the limma package. Some of them belonged to 11 biological pathways. Combined biomarkers were identified in two microarray datasets and were evaluated in a different dataset. The performance of the predictive models using the combined biomarkers was superior to those of models using a single gene. When two genes were combined, the most predictive gene set in the evaluation dataset was ATR and PRKCB when linear discriminant analysis was applied. Conclusions Combined biomarkers showed good performance in predicting the risk of AD. The constructed predictive nomogram using combined biomarkers could easily be used by clinicians to identify high-risk individuals so that more efficient trials could be designed to reduce the incidence of AD.

• 대한치매학회지
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• 제22권3호
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• pp.87-99
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• 2023

Background and Purpose: According to the amyloid cascade hypothesis, fibrillary amyloid-beta load in the brain causes Alzheimer's disease (AD) with toxic effects. Recently, perivascular spaces (PVSs), fluid-filled cavities around small penetrating arterioles and venules in the brain, and the glymphatic system relationship with type 2 diabetes mellitus (DM2) and AD has been an important research topic from a physiopathological point of view. There are two types of PVSs that are associated with sporadic atherosclerosis and cerebral amyloid angiopathy. In this study, we evaluated the relationship between the number and localization of enlarged PVSs in AD. Methods: A total of 254 patients with AD and 125 healthy controls were included in this study All the patients were evaluated with neurological and cognitive examinations and magnetic resonance imaging (MRI). PVSs on MRI were graded by recording their number and location. The study was a retrospective study. Results: In our study, the number of white matter convexity-central semiovale localized PVSs was higher in patients than in the control group. In addition, the number of PVSs in this localization score was higher in patients with DM2. Cerebral PVS counts were higher in patients with AD than in the control group. Conclusions: These results suggest the important role of cerebral amyloid angiopathy, one of the vascular risk factors, and the glymphatic system in the pathogenesis of AD. In addition, the results of our study suggest that the evaluation of PVSs levels, especially at the (centrum semiovale), using imaging studies in AD is a potential diagnostic option.

• 대한치매학회지
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• 제16권3호
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• pp.72-77
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• 2017

Background and Purpose Although sleep disturbances are common and considered a major burden for patients with Alzheimer's disease (AD), the fundamental mechanisms underlying the development and maintenance of sleep disturbance in AD patients have yet to be elucidated. The aim of this study was to examine the correlation between regional cerebral blood flow (rCBF) and sleep disturbance in AD patients using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). Methods A total of 140 AD patients were included in this cross-sectional study. Seventy patients were assigned to the AD with sleep loss (SL) group and the rest were assigned to the AD without SL group. SL was measured using the sleep subscale of the Neuropsychiatric Inventory. A whole-brain voxel-wise analysis of brain SPECT data was conducted to compare the rCBF between the two groups. Results The two groups did not differ in demographic characteristics, severity of dementia, general cognitive function, and neuropsychiatric symptoms, with the exception of sleep disturbances. The SPECT imaging analysis displayed decreased perfusion in the bilateral inferior frontal gyrus, bilateral temporal pole, and right precentral gyrus in the AD patients with SL group compared with the AD patients without SL group. It also revealed increased perfusion in the right precuneus, right occipital pole, and left middle occipital gyrus in the AD with SL group compared with the AD without SL group. Conclusions The AD patients who experienced sleep disturbance had notably decreased perfusion in the frontal and temporal lobes and increased rCBF in the parietal and occipital regions. The findings of this study suggest that functional alterations in these brain areas may be the underlying neural correlates of sleep disturbance in AD patients.

• BMB Reports
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• 제42권8호
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• pp.475-481
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• 2009

Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer's disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second major mechanism of cognitive impairment has been linked to obesity and Type 2 diabetes (T2DM). Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production.

• 동의신경정신과학회지
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• 제21권1호
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• pp.71-88
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• 2010

Objectives: This research investigates the effect of the DHJHT extract on Alzheimer's disease. Specifically, the effects of the DHJHT extract on (1) the behavior (2) the infarction area of the hippocampus, and brain tissue injury in AD mice induced with ${\beta}A$ were investigated. Methods: The effects of the DHJHT extract on the proinflammation cytokines mRNA expression and production of BACE, APP and ${\beta}A$ in in BV2 microglial cell line treated by lipopolysacchaide(LPS) plus ${\beta}A$ were investigated. The effects of the DHJHT extract on the behavior of the memory deficit mice induced by scopolamine were investigated. Results: 1. The DHJHT extract suppressed the expression of IL-$1{\beta}$, IL-6, TNF-$\alpha$, COX-2, and NOS-II, BACE and APP mRNA in BV2 microglial cell line treated by LPS plus ${\beta}A$. 2. The DHJHT extract suppressed the expression of ${\beta}A$ production in BV2 microglial cell line treated with LPS plus ${\beta}A$. 3. The DHJHT extract showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. 4. The DHJHT group suppressed the expression of IL-$1{\beta}$, TNF-$\alpha$, MDA, and CD68+/CD11b+ in the brain tissue of the mice with AD induced by ${\beta}A$. 5. The DHJHT group reduced the infarction area of hippocampus, and controlled the injury of the brain tissue in the mice with AD induced by ${\beta}A$. 6. The DHJHT group reduced tau protein, and GFAP in the brain tissue of the mice with AD induced by ${\beta}A$. Conclusions: These results suggest that the DHJHT group may be effective for the treatment of AD. Thus, DHJHT could be considered among the future therapeutic drugs indicated for the treatment of AD.

• 동의신경정신과학회지
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• 제20권2호
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• pp.1-17
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• 2009

Objectives : Alzheimer's disease(AD) is the most common form of dementia, which is characterized by progressive deterioration of memory and higher cortical functions that ultimately results in total degradation of intellectual and mental activities. Nokyongdaebo-tang(Lurongdabutang) has been usually used for the treatment for the deficiency syndrome dementia and amnesia. This experiment was designed to investigate the effect of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on pathological AD model. Methods : The effects of the Nokyongdaebo-tang(Lurongdabutang) hot water extract on cultured spinal cord cells induced by ${\beta}$-amyloid were investigated. The effects of the Nokyongdaebo-tan(Lurongdabutang) hot water extract on the memory deficit mice induced by scopolamine were investigated. Results : 1. ${\beta}$-amyloid treatment on cultured spinal cord cells increased both GFAP-staining intensity of astrocytes and caspase 3 immunoreactivity on cultured cells. Then, Nokyongdaebo-tang(Lurongdabutang) treatment reduced the labeling intensity for both GFAP and caspase 3 proteins in culture cells. 2. Scopolamine treatment into mice increased levels of GFAP-positive astrocytes and caspase 3-labeled cells of the hippocampal subfields dentate hilar region, CA3 and CA1 area. In vivo administration of Nokyongdaebo-tang(Lurongdabutang) attenuated labeling intensity for those two proteins in the same hippocampal areas. Similar effects were observed by the treatment of galanthamine, an inhibitor of acetylcholinesterase. Conclusions : This experiment shows that the Nokyongdaebo-tang(Lurongdabutang) may play a protective role in damaged neural tissues. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. Nokyongdaebo-tang(Lurongdabutang) might be effective for the prevention and treatment of AD.

• Asian-Australasian Journal of Animal Sciences
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• 제29권6호
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• pp.782-792
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• 2016

As the most common neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken. In this study, a total of 121 and 70 published human ADM and PDM were identified, respectively. Thirty-seven miRNAs were co-regulated in AD and PD. We identified a total of 105 unrepeated human ADM and PDM that had at least one 100% identical animal homolog, among which 81 and 54 showed 100% sequence identity with 241 and 161 domestic animal miRNAs, respectively. Over 20% of the total mature horse miRNAs (92) showed perfect matches to AD/PD-associated miRNAs. Pigs, dogs, and cows have similar numbers of AD/PD-associated miRNAs (63, 62, and 59). Chickens had the least number of perfect matches (34). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that humans and dogs are relatively similar in the functional pathways of the five selected highly conserved miRNAs. Taken together, our study provides the first evidence for better understanding the miRNA-AD/PD associations in domestic animals, and provides guidance to generate domestic animal models of AD/PD to replace the current rodent models.

• 생물정신의학
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• 제12권2호
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• pp.98-106
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• 2005

Objectives:Donepezil is a widely used drug for the treatment of patients with Alzheimer's disease(AD). The aim of the present study was to clarify the efficacy and the characteristics of responders to donepezil. Methods:Patients with probable AD(n=80;75.7 years) and small vessel dementia(SVD)(n=18;77.8 years) who received donepezil were retrospectively analyzed using Alzheimer's registry, and three questions were asked:1) Does donepezil therapy improves cognitive symptoms in patients with dementia? 2) If donepezil improves cognitive symptoms, which items of the K-MMSE are improved? 3) What are the characteristics of responder to donepezil medication? Results:1) After donepezil medication, cognitive function measured by the K-MMSE was significantly improved in both types of dementia(AD and SVD), However, statistical differences were not found between these groups. 2) In a clinical trial of donepezil, the patients performed better than before mediation on K-MMSE items assessing orientation, recall, construction, concentration, calculation. 3) In AD, the K-MMSE score before medication was closely related with response of donepezil. Conclusion:This study suggests that donepezil improves various cognitive functions in both types of dementia, and the responsive group had significantly lower K-MMSE scores than the non-responsive group before medication.

• Journal of Acupuncture Research
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• 제23권3호
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• pp.117-127
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the following 4 structural changes : Atrophy of the Cortex, Parasympathetic, and other neural cells, the existence of Neurofibrillary tangles (NFTs), and the accumulation of Senile plaques. NFTs and Senile plaques is known to be the index of this disease. Senile plaques disturbs the neutro transmission and depletes of Acetylcholine. So, Recovery of Acetylcholine is the primal objective for treating Alzheimer's disease. So, Inhibiting the activity of Acetylcholine Esterase (AChE), which causes the hydrolysus of acetylcholine into choline and acetate, can be seen as a key role for treating Alzheimer's disease. Increasing body of evidence has been demonstrated that Bee Venom Acupuncture (BV) could compete with complex protein involving in multiple step of $NF-_{\kappa}B$ activation and exert the anti-inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-_{\kappa}B$. BV dose-dependently attenuated Scopolamine-induced Acetylcholine esterase activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.