Apoe2 Case Study

Alzheimer 's disease (AD) was discovered by a German doctor Alois Alzheimer in 1906 when he found amyloid plaques and neurofibrillary tangles in the autopsy of a woman who died of an unknown mental disease. The extracellular amyloid plaque deposits, composed of insoluble amyloid-Beta peptide were hypothesized to be the main etiological factor. “The most important abnormality is an excess of Amyloid-beta peptides brought about through either overproduction or failure in degradation.” (Uzun, Kozumplik, & Folnegović-Smalc, 2011) Later, it was discovered that intracellular neurofibrillary tangles composed of hyper-phosphorylated, helically-paired tau

Alzheimer’s is a progressive, irreversible disease that deteriorates parts of the brain, attacking neurons and nerve cells. This results in the loss of important mental functions, especially memory (Alzheimer’s Foundation of America). This disease is detrimental, both to the individual and their friends and family. Alzheimer’s is also a very dangerous disease, as those living with the condition may forget how to drive while operating a motor vehicle, forget where their home is or even forget how to breathe. Not only is Alzheimer’s a progressive and devastating disease, but is also genetic. Research has been pooling out in ways to test individuals for the Alzheimer’s gene – ApoE4 is the genetic variant that triples the risk of developing Alzheimer’s

Alzheimer’s disease known to be a neurological disorder of the central nervous system is an irreversible disorder in which brain cells deteriorate resulting to loss of our cognitive functions, primarily memory, movement coordination, reasoning and judgment, and pattern recognition. In its advanced stage, all memory and mental functioning could be lost (Healthcommunities.com, 2016). This disease is known to be caused by parts of the brain shrinking (atrophy), which destroys the structure and function of particular areas of the brain (Nhs.uk, 2016). Although the exact cause to this process is not known, research suggest that in the brains of patients with Alzheimer 's disease, scientists have found amyloid plaques (abnormal deposits of protein), neurofibrillary tangles containing tau and acetylcholine a chemical imbalances (Nhs.uk, 2016).

1.1 Dementia is an umbrella term for a range of diseases that affect memory, behaviour and motor skills. The causes vary depending on the disease but largely the presence of “plaques” and “tangles” on the neurons of the brain is found in people with Alzheimer’s. Plaques are protein that the body no longer breaks down and allows to build up; these get between the neurons and disrupt the message transmission. Tangles destroy a vital cell transport system made of proteins. The transport system is organised in orderly parallel strands like rail tracks. In healthy areas a protein call “tau” helps the tracks stay straight but in areas where tangles

Scientists believed in 1995 that there was a genetic influence in over half the cases of Alzheimer's disease. The gene scientists are giving the most consideration to apolipoprotein E gene (ApoE) as the main gene involved in the development of Alzheimer's disease. Everyone has this gene; if they did not, they would not be alive. ApoE carries a person's cholesterol through their blood. The effect that this gene has in terms of the brain is not totally understood. Scientists have found that

Tau is a protein that is found in CTE and Alzheimer's diseases and other similar tauopathies. Tau forms from the The amyloid-beta protein clumping into plaques, the build up over time attacks the nerves in your brain causing for the brain to shrink in size, to cause the affected changes in behavior or mood,being impulsive, depressed, having anxiety, changes in their thinking abilities, problems with memory, and a struggle to pay attention.

The damage then alters the permeability of the axon membrane resulting in a large inflow of calcium, and the release of apoptotic cell death mediators that may be responsible for the phosphorylation, shortening, misfolding and aggregation of tau proteins (2011). Thus, the neurodegeneration that begins in the cortical sulci and initially surrounding only small blood vessels, spreads to larger portions of the brain. This tau-toxic factor associated systemic degeneration in regions of the brain that regulate emotion, memory, and other cognitive functions, leads to the physical and neuropsychological sequelae of CTE (McKee, et al., 2010).

Background: Dementia, loss of intellectual abilities that is severe enough to interfere with social or occupational functioning, is a major socioeconomic problem. Two of the most common causes of dementia are AD (comprising 50-70% of all cases) and FTD, which makes up to 50% of dementias before age 60. Though there have been major efforts to therapeutically treat these diseases, these dementias at present are not curable. AD is characterized by early memory deficits, followed by gradual erosions of other cognitive functions. In AD, healthy brain tissue degenerates, causing a steady decline in memory and mental abilities such as abstract thinking, disorientation, loss of judgment, difficulty in performing familiar tasks, and personality changes. Several studies have suggested the importance of microtubule dependent axonal transport in dementia and that impairments in axonal transport will negatively affect the health of neurons (reviewed in Liu et al., 2012). Molecular motors such as kinesins and dynein’s transport proteins, RNAs and organelles along microtubules. Kinesin transports towards distal processes from the cell body and dynein transport from the distal processes towards cell body of neurons. Two elegant studies demonstrated that a reduction in tau protein level, a microtubule associated protein, is sufficient to improve memory loss in mouse models of neurodegenerative diseases. In the

Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disease and the most common cause of dementia. Finding the potential genes involved in AD is an essential step in molecular diagnosis and is important to understand the mechanisms leading to neurodegeneration. The genetics of early-onset AD (EOAD) are largely understood with mutations in three different genes. In contrast, the genetics of late-onset Alzheimer’s disease (LOAD) are not fully understood. LOAD is much more common and far more complex than EOAD because of the involvement of numerous genetic, epigenetic and environmental factors. The apolipoprotein E (APOE) ε4 allele has been found to be a main risk factor for LOAD. Genome-wide association studies (GWASs)

Someday it may be possible to deal with people at risk for Alzheimer's disease by keeping tau low. Consider how taking drugs that reduced cholesterol has enabled control the accumulation of cholesterol in blood vessels that results in atherosclerosis and also heart

Alzheimer’s disease is a neurodegenerative disorder, it affects two pathological hallmarks: amyloid plaques and neurofibrillary tangles. “Amyloid plaques are caused when protein pieces called beta amyloid stick together, they eventually build up between the nerve cells into plaques.” (Ballard, 2011) Amyloid plaques trigger neurological dysfunction and eventually brain death. Compared to a healthy brain the amyloid is broken down and disposed, however in AD they collect and form hard plaques. “Once brain death happens there is no way for the brain to communicate, or restore memory” (Brightfocus.org, 2014). Neurofibrillary tangles are fibers found in the brain cells, and they have a primary protein called ‘tau’ which aids in the structure called microtubule. “Microtubules help move nutrients and other factors from one cell to another with Alzheimer’ the ‘tau’ protein is abnormal and the microtubule structure collapses.” (Ballard, 2014 & Brightfocus.org, 2014) Even though we often see the effects of AD on the outside; it is a neurodegenerative disease effecting the amyloid plaques and

The two main biomarkers of AD are beta-amyloid (Aβ) and tau and are highly debated in regards to their function in AD pathophysiology. The production of beta-amyloid plaques may be due to improper functioning of the proteasome preventing the breakdown of Aβ. Support for this theory comes from research indicating that the 20S proteasome is responsible for Aβ degradation and that alterations to the kinetics of the proteasome increased Aβ levels (Zhao & Yang, 2010). These accumulated levels of Aβ plaques leads to lower levels of soluble Aβ, which is needed for memory formation. This may occur through activation of nicotinic acetylcholine (ACh) receptors and AChE levels are drastically reduced in AD patients. (Garcia-Osta & Alberini, 2009). The microtubule stabilizing protein tau may become hyper-phosphorylated in AD due to the presence of high levels of Aβ. Hoshi et al (1996) showed that Aβ exposure to rat hippocampal neurons in vitro produced increased levels of the tau kinase GSK-3 (glycogen synthase kinase 3) which in turn hyper-phosphorylated tau leading to cellular death. (Hoshi et al., 1996) The neurotoxicity of tau may not be produced solely because of GSK-3, but may be due to

APP’s protective role in TBI is currently understood to be the product of ɑ-secretase pathway in soluble amyloid precursor protein ɑ (sAPPɑ) (Corrigan et al. 2013). This pathway was discovered in the previous year by the same researchers who used APP knockout mice. The knockout mice had cognitive and motor functions that were severely compromised with impaired neuroreparative abilities compared to its wild-type counterpart (Corrigan et al. 2012). When the knockout mice were treated with sAPPɑ, however, their neuroreparative responses were restored.

Emerging evidence demonstrates neuroinflammation as a crucial pathophysiology of AD, specifically impacted by microglia and astroglia. 3 The microglia are distributed evenly across the brain and are activated by protein aggregation and neuronal cell death. 3 Specifically related to AD, the two chief proteins involved are amyloid-B and tau.3 An accumulation of microglia around amyloid-B plaques has been documented in post-mortem human brains and in animal models with AD.3 Research has yet to clearly determine if microglial activation plays a beneficial or detrimental role in the progression of AD..3 Some reports suggest that microglia are attracted to

The roles of Apo E that is synthesized in the immune system and the nervous system on lipid and lipoprotein metabolism are not well understood (Eichner et al., 2002), (Anthopoulos et al., 2010).