Genetic Interaction Between Lsd1 And Hyperphosphorylated Tau

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

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

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).

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

Alzheimer’s disease is named after Dr. Alois Alzheimer who first discovered deviations from normal tissues of healthy individuals in the brain tissue of a lady in 1906. The woman, who showed symptoms of erratic behavior, loss of memory, and problems with communication, died of a then unfamiliar mental disorder. This led Dr. Alzheimer to investigate the cause of her unusual death. He assessed the brain of the woman and found that there were many anomalous masses (amyloid plaques) and intertwined bundles of fiber (neurofibrillary tangles). Scientists today have pinpointed the qualities of Alzheimer’s to be a) tangles in the brain (neurofibrillary tangles), b) plaque in the brain (amyloid plaques), and c) loss of connections among nerve cells.

The cause of Alzheimer’s is still mostly unknown except for one to five percent where genetic mutations have been identified as the cause. However there are many competing hypotheses that try to

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

In order to effectively treat and reduce the symptoms of Alzheimer’s, we still need to learn more about b-amyloid buildup and tau protein associated neurofibrillary tangles in the brain, which are characteristic of the disease. Similarly, we need to find if these are linked to APOE4 as those who inherit APOE4 have a greater chance of developing Alzheimer’s disease because is does not break down proteins (Molenda-Figueira, 2015).

Furthermore, these fragments were only present in regions that are implicated with AD-related cognitive deficits, the hippocampus and the neocortex (Brecht et al., 2004). Shi et al. (2017)’s article follows through these results in that accumulation of phosphorylated tau was also found in an age dependent manner in AD-vulnerable regions, particularly the hippocampus (Figure 1b). Phosphorylated tau also accumulated in an ApoE isoform and age dependent manner, such that neurons overexpressing ApoE4 showed increasingly higher levels of phosphorylated tau as the mice get older but not in ApoE3 overexpressing mice (Figure 1A) (Brecht et al., 2004).

Alzheimer’s Disease is indicated by the break down of the nervous system, essentially the neurons within the brain (MacGill, 2009). The break down leads to nerve cell eradication, and the casualty of tissue throughout the brain (MacGill, 2009). As the disease progress, the brain begins to shrink fiercely, developing loss of its normal functioning (MacGill, 2009). Abnormal protein groups and structures of plaques and tangles characterize the disease (MacGill, 2009). Plagues and tangles are not able to be viewed or tested in the living brain, but are able to be observed in an autopsy of an infected deceased (MacGill, 2009).

Awareness is necessary in understanding this disease. As humans continue to live longer, the risk for many illness and deficiencies begin to present them. Alzheimer’s and dementia is one of the many problems that plague the aging population. Understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal

There are more than 5 million people in the U.S. with Alzheimer’s and it causes 500,000 deaths a year in the U.S. alone. This disease is growing quickly, by the year 2050 it is expected that there will be 16 million people diagnosed with it in the U.S. and 100 million worldwide. The goal is to overcome this disease by the year 2025, which is possible, but very challenging. A neurologist at Harvard Medical School, by the name of Rudolph Tanzi said, “We will be able to identify those most at risk based on their genetics, do imaging tests to determine the onset and then institute therapies that nip it in the bud”(Marsa). This is great news because it will help the doctors get a jumpstart on those who are at risk of getting the disease. Memory loss is the main issue of Alzheimer’s which is caused by tangles in the brain. Without the tangles there is no disease, the tangles are what cause it. Alzheimer’s also causes shrinkage to the brain. Moving ahead with a cure, researcher need to figure out how the protective mutant gene works, making a treatment to copy what it does

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).

drug in collaboration with the University of Aberdeen to inhibit the aggregation of Tau proteins

One of the primary events that are implicated in these diseases is the amassing of distinct protein-based macroscopic deposits in the brain, leading to neuronal apoptosis [7]. Alpha synuclein was found to be the major component of lewy body, which is the hallmark of degenerating neurons in Parkinson’s disease (PD) [8]; whereas Alzheimer’s disease (AD) is marked by the existence of intracellular lesions of tau which forms neuro fibrillary tangles (NFT) and extra cellular lesions called plaque, consisting β-amyloid (Aβ) peptide as a major component [9]. In ALS, cytoplasmic lesions of SOD1 protein have been found in transgenic mice over expressing mutant SOD1, leading to the development of an array of neurodegenerative changes consisting of vacuolization and swelling of mitochondria as well as axonal degeneration [10]. These deposits are a classic disease signature; although the main protein component is dissimilar in each disease, they have parallel morphological, structural, and staining