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Alzheimer's disease (AD) is the most common form of dementia. The accumulation of β-amyloid plaques and intracellular neurofibrillary tangles of hyperphosphorylated tau protein are two hallmarks of AD. The β-amyloid and tau proteins have been the center for AD research and drug development for decades. However, most of the clinical trials targeting β-amyloid have failed. Whereas the safety and efficacy of most tau-targeting drugs have not yet been completely assessed, the first tau aggregation inhibitor, LMTX, failed in a late-stage trial, leading to further recognition of the complexities of AD and reconsideration of the amyloid hypothesis, and perhaps the tau hypothesis as well, in AD. Multilevel complex interactions between genetic, epigenetic and environmental factors contribute to AD occurrence and progression. Formaldehyde (FA) is a widespread environmental organic pollutant. It is also an endogenous metabolite in the human body. Recent studies suggest that elevation of FA in the body, by endogenous and/or exogenous exposure, may play important roles in AD development. We have demonstrated that FA reduces lysine acetylation of cytosolic histones, thereby compromising chromatin assembly and resulting in the loss of histone content in chromatin, a conserved feature of aging from yeast to humans. Aging is an important factor for AD progression. Therefore, FA-induced inhibition of chromatin assembly and the loss of histones may contribute to AD initiation and/or development. This review will briefly summarize current knowledge on mechanistic insights into AD, focusing on epigenetic alterations and FA involvement in AD development. The exploration of chemical exposures as contributing factors to AD may provide new inights into AD mechanisms and could identify potential novel therapeutic targets.
This article was published in the following journal.
Name: Chemical research in toxicology
Alzheimer's disease swept every corner of the globe and the number of patients worldwide has been rising. At present, there are as many as 30 million people with Alzheimer's disease in the world, and ...
The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an o...
We tested the hypothesis that low plasma complement C3 is observationally and genetically associated with high risk of Alzheimer's disease.
To assess associations between improvements in neuropsychiatric symptoms (NPS) and neurocognitive change in patients with Alzheimer's disease (AD) during treatment using the Clinical Antipsychotic Tri...
The tau protein plays a central role in Alzheimer's disease (AD), and there is huge interest in measuring tau in blood and cerebrospinal fluid (CSF).
RATIONALE: Exposure to formaldehyde in the work place may affect the risk of developing cancer later in life. Learning about the long-term effects of formaldehyde exposure may help the stu...
The purpose of this study is to identify potential biomarkers that may predict the development of Alzheimer's disease in people who carry an Alzheimer's mutation.
This study is being done to learn about inflammation in the brain of those with Alzheimer's disease (AD). The purpose of this study is to determine if 11C-ER176 is able to accurately measu...
Currently, no cures or disease modifying therapies exist for Alzheimer's disease (AD). This is partially due to the inability to detect the disease before it has progressed to a stage wher...
Participants enrolled in the Alzheimer's Disease Clinical Core at Wake Forest School of Medicine will be invited to take part in this study. The purpose of this study is to identify and me...
Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.
Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.
A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)
A carbamate-derived reversible CHOLINESTERASE INHIBITOR that is selective for the CENTRAL NERVOUS SYSTEM and is used for the treatment of DEMENTIA in ALZHEIMER DISEASE and PARKINSON DISEASE.
A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION, POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...