Alzheimer's disease(AD) is a progressive dementia characterized by global cognitive decline and is defined pathologically by amyloid plaques and neurofibrillary tangles. In the past 10 years, important progress has been made in the understanding of the pathogenic mechanism of AD, and new therapeutic targets have become available that should allow the underlying disease process to be tackled directly. In this respect, the 'amyloid hypothesis' has been become the dominant theory in the cause of AD. New strategies for conquering the AD include attempts to stop the production of beta-amyloid protein(Abeta), increasing Abeta clearance, or interfere with Abeta aggregation and precipitation into fibril or plaques. This review summarizes recent advances in research on AD and inspects the perspective of research in potential therapies of AD.
Aged ; Alzheimer Disease* ; Amyloid ; Dementia ; Humans ; Neurofibrillary Tangles ; Plaque, Amyloid

Alzheimer's disease, the most common cause of dementia, is characterized by two major pathological hallmarks: amyloid plaques and neurofibrillary tangles. Based on these two indicators, an amyloid cascade hypothesis was proposed, and accordingly, most current therapeutic approaches are now focused on the removal of beta-amyloid peptides (Abeta from the brain. Additionally, strategies for blocking tau hyperphosphorylation and aggregation have been suggested, including the development of drugs that can block the formation of tangles. However, there are no true disease-modifying drugs in the current market, though many drugs based on theories other than Abeta and tau pathology are under development. The purpose of this review was to provide information on the current development of AD drugs and to discuss the issues related to drug development.
Alzheimer Disease ; Amyloid ; Brain ; Dementia ; Neurofibrillary Tangles ; Peptides ; Plaque, Amyloid

The pathophysiologic process of Alzheimer's disease (AD) begins years before the diagnosis of clinical dementia. This concept of preclinical AD has arisen from the observation of AD pathologic findings such as senile plaques and neurofibrillary tangles in the brains of people who at the time of death had normal cognitive function. Recent advances in biomarker studies now provide the ability to detect the pathologic changes of AD, which are antecedent to symptoms of the illness, in cognitively normal individuals. Functional and structural brain alterations that begin with amyloid-beta accumulation already show the patterns of abnormality seen in individuals with dementia due to AD. The presence of preclinical AD provides a critical opportunity for potential interventions with disease-modifying therapy. This review focuses on the studies of antecedent biomarkers for preclinical AD.
Aging ; Alzheimer Disease ; Biomarkers ; Brain ; Dementia ; Neurofibrillary Tangles ; Plaque, Amyloid

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model .
Alzheimer Disease ; Amyloid beta-Peptides ; Humans ; Neurofibrillary Tangles ; tau Proteins

Alzheimer's disease (AD) is a chronic central neurodegenerative disease. The pathological features of AD are the extracellular deposition of senile plaques formed by amyloid-β oligomers (AβOs) and the intracellular accumulation of neurofibrillary tangles formed by hyperphosphorylated tau protein. In this paper, an in vitro pathological model of AD based on neuronal network chip and its real-time dynamic analysis were presented. The hippocampal neuronal network was cultured on the microelectrode array (MEA) chip and induced by AβOs as an AD model in vitro to simultaneously record two firing patterns from the interneurons and pyramidal neurons. The spatial firing patterns mapping and cross-correlation between channels were performed to validate the degeneration of neuronal network connectivity. This biosensor enabled the detection of the AβOs toxicity responses, and the identification of connectivity and interactions between neuronal networks, which can be a novel technique in the research of AD pathological model in vitro.
Alzheimer Disease ; Amyloid beta-Peptides ; Humans ; Neurofibrillary Tangles ; tau Proteins

Alzheimer's disease (AD) without cure remains as a serious health issue in the modern society. The major neuropathological alterations in AD are characterized by chronic neuroinflammation and neuronal loss due to neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau, plaques of β-amyloid (Aβ) and various metabolic dysfunctions. Due to the multifaceted nature of AD pathology and our limited understanding on its etiology, AD is difficult to be treated with currently available pharmaceuticals. This unmet need, however, could be met with stem cell technology that can be engineered to replace neuronal loss in AD patients. Although stem cell therapy for AD is only in its development stages, it has vast potential uses ranging from replacement therapy to disease modelling and drug development. Current progress with stem cells in animal model studies offers promising results for the new prospective treatment for AD. This review will discuss the characteristics of AD, current progress in stem cell therapy and remaining challenges and promises in its development.
Alzheimer Disease* ; Humans ; Models, Animal ; Neurofibrillary Tangles ; Neurogenesis ; Neurons ; Pathology ; Prospective Studies* ; Stem Cells* ; Transplantation

A patient presenting with the characteristic clinical features of the dementia of Pick's type is described, in whom neuropathological examination of brain biopsy material revealed atypical features, including extensive subcotical gliosis with mild cortical neuronal loss and without any neuronal cytoskeletal inclusions (Pick bodies, neurofibrillary tangles, and Lewy bodies) and amyloid deposits (senile plaques). And she has the suggestive family history of the same clinical features in her two brothers. So, the clinical and pathological features are discussed with particular reference to typical Alzheimer's disease and Pick's disease, and it is proposed that the case should be classified as familial progressive subcortical gliosis.
Alzheimer Disease ; Biopsy ; Brain ; Dementia ; Gliosis* ; Humans ; Neurofibrillary Tangles ; Neurons ; Pick Disease of the Brain ; Plaque, Amyloid ; Siblings

Alzheimer's disease (AD) is the most common etiology of dementia, that has not been previously reported in Korea. We have experienced two cases of Alzheimer's disease, one occurred in a 53-year-old man with dementia and the other occurred in a 36-year-old woman with a family history of early onset dementia. A neocortical biopsy was done to rule out the cause of dementia and showed diffusely scattered numerous senile plaques and neurofibrillary tangles in cortex of both cases. Interestingly, GFAP, an immunohistochemical stain showed strong positivity in neuritic plaques and the surrounding fibrillary gathering.
Adult ; Alzheimer Disease* ; Biopsy ; Dementia ; Female ; Humans ; Korea ; Middle Aged ; Neurofibrillary Tangles ; Plaque, Amyloid

Alzheimer's disease (AD) is the most common etiology of dementia, that has not been previously reported in Korea. We have experienced two cases of Alzheimer's disease, one occurred in a 53-year-old man with dementia and the other occurred in a 36-year-old woman with a family history of early onset dementia. A neocortical biopsy was done to rule out the cause of dementia and showed diffusely scattered numerous senile plaques and neurofibrillary tangles in cortex of both cases. Interestingly, GFAP, an immunohistochemical stain showed strong positivity in neuritic plaques and the surrounding fibrillary gathering.
Adult ; Alzheimer Disease* ; Biopsy ; Dementia ; Female ; Humans ; Korea ; Middle Aged ; Neurofibrillary Tangles ; Plaque, Amyloid

BACKGROUND: Alzheimer's disease (AD) is characterized by the pathology of amyloid plaques and tau-associated neurofibrillary tangles. Acetylcholine esterase (AChE) transforms the beta-amyloid monomer into an oligomer, and increases beta-amyloid aggregation in the brain. Increased beta-amyloid breaks the cytoskeleton of the brain by hyperphosphorylation of the tau protein. Previous studies support that AChE inhibitor has an inhibitory effect on toxicity of the beta-amyloid and phophorylated tau protein. The purpose of this study was to analyze the CSF beta-amyloid 1-42 (A beta 1-42) and phosphorylated tau protein in AD and determine their difference depending on whether AChE inhibitor was taken or not. METHODS: Subjects included 16 AD, 14 normal controls, and 15 disease controls. Nine of AD group had taken an AChE inhibitor while the remainder had not. The CSF A beta 1-42 and phosphorylated tau were measured by ELISA. RESULTS: The CSF A beta 1-42 levels were lower in AD patients than in other groups (p<0.01). We also found increased CSF A beta 1-42 levels in the AChE inhibitor users, compared with non-users. CONCLUSIONS: The level of CSF A beta 1-42 may have a diagnostic value in the patients with cognitive impairments. Also, we may expect the effect of AChE inhibitor on Alzheimer's pathology by measuring CSF A beta 1-42 levels. Therefore, the level of CSF A beta 1-42 may serve as a biological surrogate marker for AD treatment.
Acetylcholine ; Alzheimer Disease ; Biomarkers ; Brain ; Cytoskeleton ; Humans ; Neurofibrillary Tangles ; Plaque, Amyloid ; tau Proteins