Alzheimer's
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Alzheimer's
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of APOE. Other risk factors include a history of head injury, clinical depression, and high blood press ...
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Dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affects a person's ability to function and carry out everyday activities. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Consciousness is not affected. Dementia ultimately has a significant effect on the individual, caregivers, and on social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning, and a greater cognitive decline than what is caused by normal aging. Several diseases and injuries to the brain, such as a stroke, can give rise to dementia. However, th ...
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Amyloid Plaques
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. Abnormal neurites in amyloid plaques are tortuous, often swollen axons and dendrites. The neurites contain a variety of organelles and cellular debris, and many of them include characteristic paired helical filaments, the ultrastructural component of neurofibrillary tangles. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve with an average plaque area of 400-450 square micrometers (µm²). The smallest plaques (less than 200 ...
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Neurodegeneration
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that ...
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Apolipoprotein E
Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular disease. APOE belongs to a family of fat-binding proteins called apolipoproteins. In the circulation, it is present as part of several classes of lipoprotein particles, including chylomicron remnants, VLDL, IDL, and some HDL. APOE interacts significantly with the low-density lipoprotein receptor (LDLR), which is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins. In peripheral tissues, APOE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism. In the central nervous system, APOE is mainly produced by astrocytes and transports cholesterol to neurons via APOE receptors, which are members of the low density lipoprotein receptor gene family. APOE is the principal cholesterol carrier in the brain. APOE is required for cholesterol transportation from astrocy ...
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Neurofibrillary Tangle
Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is known about their exact relationship to the different pathologies. Formation Neurofibrillary tangles are formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate, or group, in an insoluble form. (These aggregations of hyperphosphorylated tau protein are also referred to as PHF, or " paired helical filaments"). The precise mechanism of tangle formation is not completely understood, and it is still controversial whether tangles are a primary causative factor in disease or play a more peripheral role. Cytoskeletal changes Three different maturation states of NFT have been defined using anti-tau and anti-ubiquitin immunostaining. At stage 0 there are morphologically normal pyramidal cells showing ...
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Primary Progressive Aphasia
Primary progressive aphasia (PPA) is a type of neurological syndrome in which language capabilities slowly and progressively become impaired. As with other types of aphasia, the symptoms that accompany PPA depend on what parts of the left hemisphere are significantly damaged. However, unlike most other aphasias, PPA results from continuous deterioration in brain tissue, which leads to early symptoms being far less detrimental than later symptoms. Those with PPA slowly lose the ability to speak, write, read, and generally comprehend language. Eventually, almost every patient becomes mute and completely loses the ability to understand both written and spoken language. Although it was first described as solely impairment of language capabilities while other mental functions remain intact, it is now recognized that many, if not most of those with PPA experience impairment of memory, short-term memory formation and loss of executive functions. It was first described as a distinct syndrom ...
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Short-term Memory
Short-term memory (or "primary" or "active memory") is the capacity for holding a small amount of information in an active, readily available state for a short interval. For example, short-term memory holds a phone number that has just been recited. The duration of short-term memory (absent rehearsal or active maintenance) is estimated to be on the order of seconds. The commonly cited capacity of 7 items, found in Miller's Law, has been superseded by 4±1 items. In contrast, long-term memory holds information indefinitely. Short-term memory is not the same as working memory, which refers to structures and processes used for temporarily storing and manipulating information. Stores The idea of separate memories for short-term and long-term storage originated in the 19th century. A model of memory developed in the 1960s assumed that all memories are formed in one store and transfer to others store after a small period of time. This model is referred to as the "modal model", most ...
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Acetylcholinesterase Inhibitor
Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family. Acetylcholinesterase inhibitors are classified as reversible, irreversible, or quasi-irreversible (also called pseudo-irreversible). Mechanism of action Organophosphates Organophosphates like TEPP and sarin inhibit cholinesterases, enzymes that hydrolyze the neurotransmitter acetylcholine. The active centre of cholinesterases feature two important sites, namely the a ...
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Aging Brain
Aging is a major risk factor for most common neurodegenerative diseases, including mild cognitive impairment, dementias including Alzheimer's disease, cerebrovascular disease, Parkinson's disease, and Lou Gehrig's disease. While much research has focused on diseases of aging, there are few informative studies on the molecular biology of the aging brain (usually spelled ageing brain in British English) in the absence of neurodegenerative disease or the neuropsychological profile of healthy older adults. However, research suggests that the aging process is associated with several structural, chemical, and functional changes in the brain as well as a host of neurocognitive changes. Recent reports in model organisms suggest that as organisms age, there are distinct changes in the expression of genes at the single neuron level. This page is devoted to reviewing the changes associated with healthy aging. Structural changes Aging entails many physical, biological, chemical, and psychologic ...
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Lewy Body Dementia
Lewy body dementias are two similar and common subtypes of dementia—dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The two conditions have similar features and may have similar causes, and are believed to belong on a spectrum of Lewy body disease that includes Parkinson's disease. As of 2014, they were more often misdiagnosed than any other common dementia. The exact cause is unknown, but involves widespread deposits of abnormal clumps of protein that form in neurons of the diseased brain. Known as Lewy bodies (discovered in 1912 by Frederic Lewy) and Lewy neurites, these clumps affect both the central nervous system and the autonomic nervous system. The fifth revision of the ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM-5) gives Lewy body disease as the causative subtype of dementia with Lewy bodies, and Parkinson's disease as the causative subtype of Parkins ...
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NMDA Receptor Antagonist
NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce is referred to as dissociative anesthesia. Several synthetic opioids function additionally as NMDAR-antagonists, such as pethidine, levorphanol, methadone, dextropropoxyphene, tramadol and ketobemidone. Some NMDA receptor antagonists, such as ketamine, dextromethorphan (DXM), phencyclidine (PCP), methoxetamine (MXE), and nitrous oxide (N2O), are sometimes used as recreational drugs, for their dissociative, hallucinogenic, and euphoriant properties. When used recreationally, they are classified as dissociative drugs. Uses and effects NMDA receptor antagonists induce a state called dissociative anesthesia, marked by catalepsy, amnesia, and analgesia. Ketamine is a favored anesthetic for emergency patients with unknown medical history and i ...
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Human Brain
The human brain is the central organ of the human nervous system, and with the spinal cord makes up the central nervous system. The brain consists of the cerebrum, the brainstem and the cerebellum. It controls most of the activities of the body, processing, integrating, and coordinating the information it receives from the sense organs, and making decisions as to the instructions sent to the rest of the body. The brain is contained in, and protected by, the skull bones of the head. The cerebrum, the largest part of the human brain, consists of two cerebral hemispheres. Each hemisphere has an inner core composed of white matter, and an outer surface – the cerebral cortex – composed of grey matter. The cortex has an outer layer, the neocortex, and an inner allocortex. The neocortex is made up of six neuronal layers, while the allocortex has three or four. Each hemisphere is conventionally divided into four lobes – the frontal, temporal, parietal, and occipital lo ...
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