• BMB Reports
• /
• v.52 no.12
• /
• pp.679-688
• /
• 2019

The decrease of metabolism in the brain has been observed as the important lesions of Alzheimer's disease (AD) from the early stages of diagnosis. The cumulative evidence has reported that the failure of mitochondria, an organelle involved in diverse biological processes as well as energy production, maybe the cause or effect of the pathogenesis of AD. Both amyloid and tau pathologies have an impact upon mitochondria through physical interaction or indirect signaling pathways, resulting in the disruption of mitochondrial function and dynamics which can trigger AD. In addition, mitochondria are involved in different biological processes depending on the specific functions of each cell type in the brain. Thus, it is necessary to understand mitochondrial dysfunction as part of the pathological phenotypes of AD according to each cell type. In this review, we summarize that 1) the effects of AD pathology inducing mitochondrial dysfunction and 2) the contribution of mitochondrial dysfunction in each cell type to AD pathogenesis.

• BMB Reports
• /
• v.53 no.1
• /
• pp.10-19
• /
• 2020

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The AD pathophysiology entails chronic inflammation involving innate immune cells including microglia, astrocytes, and other peripheral blood cells. Inflammatory mediators such as cytokines and complements are also linked to AD pathogenesis. Despite increasing evidence supporting the association between abnormal inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. Since many reports have shown that abnormal inflammation precedes the outbreak of the disease, non-invasive and readily available peripheral inflammatory biomarkers should be considered as possible biomarkers for early diagnosis of AD. In this minireview, we introduce the peripheral biomarker candidates related to abnormal inflammation in AD and discuss their possible molecular mechanisms. Furthermore, we also summarize the current state of inflammatory biomarker research in clinical practice and molecular diagnostics. We believe this review will provide new insights into biomarker candidates for the early diagnosis of AD with systemic relevance to inflammation during AD pathogenesis.

• Biomedical Science Letters
• /
• v.25 no.1
• /
• pp.7-14
• /
• 2019

Alzheimer's disease (AD) is highly prevalent in dementia, with no specifically effective treatment having yet been discovered. Amyloid plaques are one of the key hallmarks of AD. Transgenic mouse models exhibiting Alzheimer's disease-like pathology have been widely used to study the pathophysiology of Alzheimer's disease. In this study, we showed an age-dependent correlation between cognitive function, pathological findings, and [F-18] Florbetaben (FBB) PET images. Nineteen transgenic mice (12 with AD, 7 with controls) were used for this study. We observed an increase in ${\beta}$-Amyloid deposition ($A{\beta}$) in brain tissue and [F-18] FBB amyloid PET imaging in the AD group. The [F-18] FBB data showed a mildly negative trend with cognitive function. Pathological findings were negatively correlated with cognitive functions. These finding suggests that amyloid beta deposition can be well-monitored with [F-18] FBB PET and a decline in cognitive function is related to the increase in amyloid plaque burden.

• BMB Reports
• /
• v.49 no.6
• /
• pp.337-343
• /
• 2016

Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy.

• Herbal Formula Science
• /
• v.11 no.2
• /
• pp.95-110
• /
• 2003

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions in study Jeonmaedan have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet fully elucidated. It has been widely believed that A${\beta}$ peptide devided from APP causes apoptotic neurotoxicity in AD brain. However, recent evidence suggests that CTl05(carboxy terminal 105 amino acid peptide fragment of APP) may be an important factor causing neurotoxicity in AD. In addition, AD is one of brain degeneration disease. So we studied on herbal medicine that have a relation of brain degeneration. In Oriental Medicine, Jeonmaedan has been used for disease in relation to brain degeneration. As the result of this study, in Jeonmaedan the apoptosis in the nervous system is inhibited, the repair against the degerneration of SK-N-SH cell lines by CT105 expression is promoted. So Jeonmaedan may be beneficial for the treatment of AD.

• Journal of Biomedical Engineering Research
• /
• v.44 no.6
• /
• pp.377-383
• /
• 2023

Purpose: There is increasing attention to the application of transcranial direct current stimulation (tDCS) for enhancing cognitive functions in subjects to aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Despite varying treatment outcomes in tDCS which depend on the amount of current reaching the brain, there is no general information on the impacts of anatomical features associated with AD on tDCS-induced electric field. Objective: The objective of this study is to examine how AD-related anatomical variation affects the tDCS-induced electric field using computational modeling. Methods: We collected 180 magnetic resonance images (MRI) of AD patients and healthy controls from a publicly available database (Alzheimer's Disease Neuroimaging Initiative; ADNI), and MRIs were divided into female-AD, male-AD, female-normal, and male-normal groups. For each group, segmented brain volumes (cerebrospinal fluid, gray matter, ventricle, rostral middle frontal (RMF), and hippocampus/amygdala complex) using MRI were measured, and tDCS-induced electric fields were simulated, targeting RMF. Results: For segmented brain volumes, significant sex differences were observed in the gray matter and RMF, and considerable disease differences were found in cerebrospinal fluid, ventricle, and hippocampus/amygdala complex. There were no differences in the tDCS-induced electric field among AD and normal groups; however, higher peak values of electric field were observed in the female group than the male group. Conclusions: Our findings demonstrated the presence of sex and disease differences in segmented brain volumes; however, this pattern differed in tDCS-induced electric field, resulting in significant sex differences only. Further studies, we will adjust the brain stimulation conditions to target the deep brain and examine the effects, because of significant differences in the ventricles and deep brain regions between AD and normal groups.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.6
• /
• pp.447-456
• /
• 2014

Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) $A{\beta}_{1-42}$, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the clinical utility of CSF biomarkers and the integration of CSF biomarkers in current clinical trials.

• Journal of Korea Multimedia Society
• /
• v.24 no.5
• /
• pp.667-675
• /
• 2021

The treatments for symptoms of Alzheimer's disease are being provided and for the early diagnosis several researches are undergoing. In this regard, by using T1-weighted images several classification techniques had been proposed to distinguish among AD, MCI, and Healthy Control (HC) patients. In this paper, we also used some traditional Machine Learning (ML) approaches in order to diagnose the AD. This paper consists of an improvised feature selection method which is used to reduce the model complexity which accounted an issue while utilizing the ML approaches. In our presented work, combination of subcortical and cortical features of 308 subjects of ADNI dataset has been used to diagnose AD using structural magnetic resonance (sMRI) images. Three classification experiments were performed: binary classification. i.e., AD vs eMCI, AD vs lMCI, and AD vs HC. Proposed Feature Selection method consist of a combination of Principal Component Analysis and Recursive Feature Elimination method that has been used to reduce the dimension size and selection of best features simultaneously. Experiment on the dataset demonstrated that SVM is best suited for the AD vs lMCI, AD vs HC, and AD vs eMCI classification with the accuracy of 95.83%, 97.83%, and 97.87% respectively.

• BMB Reports
• /
• v.53 no.1
• /
• pp.47-55
• /
• 2020

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease and has become a major socioeconomic issue in many developed countries. Currently available therapeutic agents for AD provide only symptomatic treatments, mainly because the complete mechanism of the AD pathogenesis is still unclear. Although several different hypotheses have been proposed, mitochondrial dysfunction has gathered interest because of its profound effect on brain bioenergetics and neuronal survival in the pathophysiology of AD. Various therapeutic agents targeting the mitochondrial pathways associated with AD have been developed over the past decade. Although most of these agents are still early in the clinical development process, they are used to restore mitochondrial function, which provides an alternative therapeutic strategy that is likely to slow the progression of the disease. In this mini review, we will survey the AD-related mitochondrial pathways and their small-molecule modulators that have therapeutic potential. We will focus on recently reported examples, and also overview the current challenges and future perspectives of ongoing research.

• Korean Journal of Biological Psychiatry
• /
• v.18 no.1
• /
• pp.36-45
• /
• 2011

Objectives : Though a proportion of Alzheimer's disease(AD) patients treated with donepezil have shown positive response on cognition, but the responders' characteristics are still uncertain. This study attempts to identify whether a single oral dose of donepezil(5mg) can change cognition and the relationship between single dose responder items and long-term responder are examined. Methods : Twenty-three AD patients for single donepezil challenge study group and eleven AD patients for controls were participated in the study. Seven days after baseline study for neuropsychological test and EEG, same studies were rechecked after donepezil medication in study group. In donepezil study groups, 12 weeks after donepezil medication, neuropsychological test and EEG were rechecked. Results : After single donepezil challenge, forward digit span, Rey-Osterrieth Complex Figure Test copy, SVLT delayed recall were significantly improved, and beta spectra power in anterior, theta spectra power in posterior field were significantly decreased. According to linear regression analysis, forward digit span after single donepezil challenge was significantly positive correlated with long-term responders. Conclusions : This study suggests that single donepezil medication can significantly change cognitive functions and EEG in AD patients. Among these responsive items, forward digit span was significantly correlated with long-term responder.