• Proceedings of the Korean Society of Medical Physics Conference
• /
• 2003.09a
• /
• pp.46-46
• /
• 2003

Several MRI studies have reported reductions in temporal lobe volumes in Alzheimer´s disease (AD). Measures have been usually obtained with regions of interest (ROI) drawn manually on selected medial and lateral portions of the temporal lobes, with variable choices of anatomical borders across different studies. We used the automated voxel based morphometry (VBM) approach to investigate gray matter abnormalities over the entire extension of the temporal lobe in 11 AD patients (MMSE 14 - 25) and 11 healthy controls. Foci of significantly reduced gray matter volume in AD patients were detected in both medial and lateral temporal regions, most significantly in the right and left posterior parahippocampal gyri. At a more flexible statistical threshold (P<0.001, uncorrected for multiple comparisons), circumscribed foci of significant gray matter reduction were also detected in the right amygdala/enthorinal cortex, the anterior and posterior borders of the superior temporal gyrus bilaterally, and the anterior portion of the left middle temporal gyrus. These VBM results confirm previous findings of temporal lobe atrophic changes in AD, and suggest that these abnormalities may be confined to specific sites within that lobe, rather than showing a widespread distribution.

• Biomolecules & Therapeutics
• /
• v.20 no.3
• /
• pp.245-255
• /
• 2012

Amyloid-${\beta}$ peptide ($A{\beta}$) is still best known as a molecule to cause Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. Thus, strategies on developing AD drugs have been focused on the reduction of $A{\beta}$ in the brain. Since accumulation of $A{\beta}$ depends on the rate of its synthesis and clearance, the metabolic pathway of $A{\beta}$ in the brain and the whole body should be carefully explored for AD research. Although the synthetic pathway of $A{\beta}$ is equally important, we summarize primarily the clearance pathway in this paper because the former has been extensively reviewed in previous studies. The clearance of $A{\beta}$ from the brain is accomplished by several mechanisms which include non-enzymatic and enzymatic pathways. Nonenzymatic pathway includes interstitial fluid drainage, uptake by microglial phagocytosis, and transport across the blood vessel walls into the circulation. Multiple $A{\beta}$-degrading enzymes (ADE) implicated in the clearance process have been identified, which include neprilysin, insulin-degrading enzyme, matrix metalloproteinase-9, glutamate carboxypeptidase II and others. A series of studies on $A{\beta}$ clearance mechanism provide new insight into the pathogenesis of AD at the molecular level and suggest a new target for the development of novel therapeutics.

• Molecules and Cells
• /
• v.42 no.11
• /
• pp.739-746
• /
• 2019

Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

• Dementia and Neurocognitive Disorders
• /
• v.21 no.1
• /
• pp.17-29
• /
• 2022

Background and Purpose: Verbal and nonverbal fluency tests are the conventional methods for examining executive function in the elderly population. However, differences in impairments result in fluency tests in patients with mild cognitive impairments (MCIs) and Alzheimer's disease (AD) and in neural correlates underlying the tests still necessitate concrete evidence. Methods: We compared the test performances in 27 normal controls, 28 patients with MCI, and 20 with AD, and investigated morphological changes in association with the test performances using structural magnetic imaging. Results: Patients with AD performed poorly across all the fluency tests, and a receiver operating characteristics curve analysis revealed that only category fluency test discriminated all the 3 groups. Association, category, and design fluency tests involved temporal and frontal regions, while letter fluency involved the cerebellum and caudate. Conclusions: Category fluency is a reliable measure for screening patients with AD and MCI, and this efficacy might be related to morphological correlates that underlie semantic and executive processing.

• Microbiology and Biotechnology Letters
• /
• v.44 no.3
• /
• pp.383-390
• /
• 2016

Mesenchymal stem cells (MSCs) are multipotent stem cells that can be differentiated into a variety of cell types, including adipocytes, osteoblasts, chondrocytes, β-pancreatic islet cells, and neuronal cells. MSCs have been reported to exhibit immunomodulatory effects in many diseases. Many studies have reported that MSCs have distinct roles in modulating inflammatory and immune responses by releasing bioactive molecules. Exosomes are cell-derived vesicles present in biological fluids, including the blood, urine, and cultured medium of cell cultures. In this study, we investigated the immunomodulatory effects of mouse adipose tissue-derived MSCs (mAD-MSCs), cultured medium (MSC-CM) of mAD-MSCs, and mAD-MSC-derived exosomes (MSC-Exo) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. We observed that the expression levels of IL-1β, TNF-α, and IL-10 were significantly increased in LPS-stimulated RAW 264.7 cells compared to those in LPS-unstimulated RAW 264.7 cells. Additionally, these values were significantly (p < 0.05) decreased in mAD-MSCs-RAW 264.7 cell co-culture groups, MSC-CM-treated groups, and MSC-Exo-treated groups. MSCs can modulate the immune system in part by secreting cytokines and growth factors. We observed that immunomodulatory factors such as IL-1β, TNF-α, and IL-10 were secreted by mAD-MSCs under co-culturing conditions of mAD-MSCs with activated RAW 264.7 cells. In addition, mAD-MSC-derived exosomes exhibited similar immunomodulatory effects in activated RAW 264.7 cells. Therefore, our results suggest that mAD-MSCs have an immunomodulatory function through indirect contact.

• BMB Reports
• /
• v.42 no.8
• /
• pp.475-481
• /
• 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.

• Journal of Yeungnam Medical Science
• /
• v.35 no.1
• /
• pp.1-6
• /
• 2018

Alzheimer's disease (AD) is a neurodegenerative disorder associated with extracellular plaques, composed of amyloid-beta ($A{\beta}$), in the brain. Although the precise mechanism underlying the neurotoxicity of $A{\beta}$ has not been established, $A{\beta}$ accumulation is the primary event in a cascade of events that lead to neurofibrillary degeneration and dementia. In particular, the $A{\beta}$ burden, as assessed by neuroimaging, has proved to be an excellent predictive biomarker. Positron emission tomography, using ligands such as $^{11}C$-labeled Pittsburgh Compound B or $^{18}F$-labeled tracers, such as $^{18}F$-florbetaben, $^{18}F$-florbetapir, and $^{18}F$-flutemetamol, which bind to $A{\beta}$ deposits in the brain, has been a valuable technique for visualizing and quantifying the deposition of $A{\beta}$ throughout the brain in living subjects. $A{\beta}$ imaging has very high sensitivity for detecting AD pathology. In addition, it can predict the progression from mild cognitive impairment to AD, and contribute to the development of disease-specific therapies.

• Smart Media Journal
• /
• v.12 no.7
• /
• pp.52-58
• /
• 2023

Alzheimer's disease is one type of dementia, the symptoms can be treated by detecting the disease at its early stages. Recently, many computer-aided diagnosis using magnetic resonance image(MRI) have shown a good results in the classification of AD. Taken these MRI images and feed to Free surfer software to extra the features. In consideration, using T1-weighted images and classifying using the convolution neural network (CNN) model are proposed. In this paper, taking the subjects from ADNI of subcortical and cortical features of 190 subjects. Consider the study to reduce the complexity of the model by using the single layer in the Res-Net, VGG, and Alex Net. Multi-class classification is used to classify four different stages, CN, EMCI, LMCI, AD. The following experiment shows for respective classification Res-Net, VGG, and Alex Net with the best accuracy with VGG at 96%, Res-Net, GoogLeNet and Alex Net at 91%, 93% and 89% respectively.

• Korean Journal of Biological Psychiatry
• /
• v.20 no.3
• /
• pp.104-110
• /
• 2013

Objectives : The aim of this study was to examine the prospective impact of the apolipoprotein E (APOE) ${\varepsilon}4$ on cognitive performance in the community-dwelling elderly individuals with Alzheimer's disease (AD). Methods : The total number of subjects was 30 (12 men and 18 women) who were diagnosed with AD from a Korean project of "Early Detection of Dementia". People aged 65-85 years were included in the analysis. The eight neuropsychological domains from the Korean version of Consortium to Establish a Registry of Alzheimer's Disease (CERAD-K) were conducted to test subjects. They have been followed at 24-month intervals with the same assessments at each interval. Their cognitive performance at 2 year intervals was compared by the occurrence of the APOE ${\varepsilon}4$. Results : The impact of ${\varepsilon}4$ allele was significant in the Word List Memory Test (WLMT, F = 4.345, df = 1, p = 0.021) and Word List Recall Test (WLRT, F = 5.569, df = 1, p = 0.033). Conclusions : The APOE ${\varepsilon}4$ allele was significantly correlated especially with verbal episodic memory domain in community-dwelling elders diagnosed with AD.

• BMB Reports
• /
• v.43 no.10
• /
• pp.656-663
• /
• 2010

Amyloid precursor protein (APP), which is critically involved in the pathogenesis of Alzheimer's disease (AD), is cleaved by gamma/epsilon-secretase activity and results in the generation of different lengths of the APP Intracellular C-terminal Domain (AICD). In spite of its small size and short half-life, AICD has become the focus of studies on AD pathogenesis. Recently, it was demonstrated that AICD binds to different intracellular binding partners ('adaptor protein'), which regulate its stability and cellular localization. In terms of choice of adaptor protein, phosphorylation seems to play an important role. AICD and its various adaptor proteins are thought to take part in various cellular events, including regulation of gene transcription, apoptosis, calcium signaling, growth factor, and $NF-{\kappa}B$ pathway activation, as well as the production, trafficking, and processing of APP, and the modulation of cytoskeletal dynamics. This review discusses the possible roles of AICD in the pathogenesis of neurodegenerative diseases including AD.