Astrocytes 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 Disease is a progressive neurological disease; it often attacks the brain tissues causing memory loss of one’s identity and regular behaviors. Statistics indicates that the rate of predicted people to get Alzheimer’s will increase briskly as time goes on. There are currently no cures for such disastrous disease, but there are currently approved treatments available that can help people within the early stages of Alzheimer’s. Once the disease is too far along, deteriorated brain cells are nearly impossible to revived or regenerate without stem cells, which have not been successfully ascertain. Research and medical trials are being conducted all over the world hoping to find the starting cause of it in

2010). The neuroinflammation is an early, non-specific immune reaction to tissue damage or pathogen invasion (Lee et al. 2010). Inflammation of the central nervous system (CNS) is characterized by increased glial activation, pro-inflammatory cytokine concentration, blood-brain-barrier permeability, and leukocyte invasion (Lee et al. 2010). Microglia are cells that support and protect neuronal functions (Lee at al. 2010). They act as the first and main form of active immune defense that orchestrate the endogenous immune response of the Central Nervous System. The microglia play a central role in the cellular response to pathological lesions such as Aβ. Aβ can attract and activate microglia, leading to clustering of microglia around Aβ deposits sites in the brain (Lee et al. 2010). Even though microglia have neuroprotective functions, neurotoxic mechanisms which involves continuous activation of microglia and toxic factors are released by microglia, which may lead to neuroinflammation (Lee et al. 2010). Astrocytes (star-shaped glial cells) are the most abundant cells in the brain and are located in the brain and spinal. Astrocytes have various functions such as: biochemical support of endothelial cells of the BBB, supplying nutrients to the nervous tissue, maintenance of extracellular ion balance, and healing the brain and spinal cord following traumatic injury (Lee et al., 2010). Chemokines are released by astrocytes which attract microglia and they further express proinflammatory products, thus increasing neuronal damage in the pathogenesis of AD (Lee et al., 2010). Astrocytes play a critical role in Aß clearance and degradation, and they also provide trophic support to neurons forming a protective barrier between Aß deposits and neurons (Wyss-Coray et al., 2003). Neurons contribute to the production of

When testing for Alzheimer’s, a patient must show a decline in at least two of these categories, which is significant enough to interfere with regular function. Alzheimer’s specialists have been working on new ways to diagnose the disease as early as possible. Specialists have discovered that they can measure the amount of beta-amyloid in the cerebrospinal fluid (Chertkow, etc. all, 2013). These “sticky” beta-amyloid plaques that build up in the brain have been proven to affect memory. It is now known that the buildup of these plaques can cause nerve cell damage (Nierenberg,

Alzheimer’s is an irreversible disease normally affecting the elderly population and is progressive in nature causing degeneration that leads to impairments in memory, reasoning, planning, and behaviour. It is a neurodegenerative disorder that adversely affects neurons in the brain, ultimately resulting in loss of memory and language, behavioural disturbances, and dependence on caregivers (Phillips, Baktir, Das, Lin & Salehi, 2015, p. 1047). Alzheimer’s has 3

Under normal condition tau binds to microtubules, stabilizing neuronal structure and integrity. Hyperphosphorylation of tau is assumed to be the cause of the formation of paired helical filaments - neurofibrillary tangles (NFT). The principle components of the senile plaques are neurofibrillary tangles in the cell bodies, neuropil threads, and neurites as well as extracellular A-beta amyloid. These lesions are surrounded by microglial and astrocytes. The brain regions affected by Alzheimer’s disease also contain neuritic or senile plaques in which extracellular deposits of amyloid are surrounded by dystrophic axons as well as the process of astrocytes and microglia. The principle constituent of amyloid is a 4kDa peptide called A-beta amyloid. A-beta amyloid is cleaved from a larger precursor protein called amyloid precursor protein. Similar abnormalities occur in transgenic mice with mutant APP and in individuals with Alzheimer’s

Scientists believe that the combinations of genetics, environmental factors, and lifestyle play a huge part in Alzheimer’s disease. Scientists are learning that age-related changes may harm neurons. These changes include shrinking of the brain, and inflammation. In early-onset genetic mutation is usually the cause, and people thirty to sixty represent less than five percent of people with Alzheimer’s disease. In late-onset

“Alzheimer’s Disease (AD) is a type of dementia, which is affecting the population that develops in the brain and can lead to problems with memory, thinking and behavior”. The Amyloid Hypothesis claims that the build up of the beta-amyloid in the brain is a cause in the development of Alzheimer disease in patients. This plaque of the beta-amyloid and its cascade of events can be linked to the deterioration and negative effects of cognitive function of the brain over time. The beta-amyloid is described to be a “sticky” protein located in the brain therefore plaques or build up of the amyloid is common. These plaques in turn can block the brain cells from communicating with each other. Which then activates an immune system, that leads to inflammation

Main reason for cognition decline could be buildup of plaque and dysfunctional proteins in the brain interfering with neuronal function. Alzheimer’s disease (AD) is an age-related neurodegenerative disease that accounts for more than 60 % of all dementia cases. The disease is characterized by cognitive deficits and memory loss through a process that lead to the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). This plaque is composed of abnormally hyperphosphorylated tau protein in the brain. Amyloid beta (Aβ or Abeta) is a peptide of 36–43 amino acids, forms amyloid plaques in the brain and are toxic to nerve cells. These peptides result from the amyloid precursor protein (APP), which is cleaved

Alzheimer’s disease (AD) is a neurodegenerative disorder involving senile plaques distributed throughout the cerebral cortex and intracellular neurofibrillary tangles. These plaques are predominantly composed of beta-amyloid (Aβ), which is a 39 to 42 amino acid peptide and is cleaved from the (APP). With 1 in every 14 people over the age of

This paper reviews how Alzheimer’s disease will slowly weaken and destroy the neuron connections within the brain. Data was assessed from four articles correlating to how a healthy brain functions in opposition to a brain with onset Alzheimer’s disease. It will analyze how and what causes the brain to shrink and disintegrate. The following articles written by (Francesco Angelucci, 2014; Christina E. Wierenga and Mark W. Bondi, 2011; Carl Banner, 1992, Richard J. Perrin, 2009) were evaluated and will go over basic brain structures, the neurons forest in relation to cell signaling, and damage to the brain with the progression of this illness.

Alzheimer's disease is a degenerative neurological disorder that is now the sixth leading cause to death in the United States. In the recent years several genes have been pinpointed that are responsible for the disorder, along with twenty genes that have been known to increase and decrease the risk of getting it. Although this newly learned information is helpful it does not fully explain the cause. Scientists have been searching relentlessly to find the explanation to onset Alzheimer's.

Importantly synaptic dysfunction occurs early in AD, while actual loss of synapses does not appear until much later in the disease. The loss of synaptic density leads to inhibition of the excitatory transmission in both the hippocampus and cerebral cortex, leading to significant memory loss [54, 55]. Although Aβ deposition and tau phosphorylation may induce neuronal loss, the predominant mechanism accounting for-synaptic thinning is more likely progressive neuronal apoptosis. Several factors have been shown to stimulate apoptosis in various models of AD, including, impaired glucose metabolism, excitotoxicity and mitochondrial dysfunction. Additionally, factors, such as tumor suppressor protein p53, forkhead box protein (FOXO), and ROS, can mediate apoptosis in AD [56, 57]. Thus, new treatment strategies aimed at developing molecules that downregulate apoptosis are currently a primary

In addition, we wanted to assess whether astrocytes, the main ECM producers in the brain, become reactive already during this early stage of AD-like disease, thereby possibly contributing to the observed ECM alterations. Our preliminary results suggest no change in the expression of basigin, a downregulation of versican and tenascin-R, and an upregulation of HAPLN1 and glial fibrillary acidic protein (GFAP) in the hippocampus of APP/PS1 mice at 3 months (early AD). Although these changes are not completely in line with previously reported ECM alterations, we do find changes in hippocampal ECM in 3 months old APP/PS1 mice that may contribute to alterations in cell communication, neuronal survival, and synaptic function and plasticity. In addition, the observed increase in GFAP expression in the hippocampus of 3 months old APP/PS1 mice and in isolated hippocampal astrocytes in vitro suggests that astrogliosis precedes amyloid plaque deposition, thus astrocytes possibly play a role in early ECM

and Mattson, 2011), and impairments of axonal transport and mitochondrial functions (Decker et al., 2010; Querfurth and LaFerla, 2010; Sheng and Cai, 2012). In addition, several lines of evidence suggest that Aβ regulates neuronal and synaptic activities and that its accumulation in the brain causes aberrant network activity and synaptic depression (Palop and Mucke, 2010). Impairments of inhibitory interneurons and aberrant stimulation of glutamate receptors result in excitotoxicity, and play important upstream roles in this pathogenic cascade. These impairments also lead to a positive feedback loop, where aberrant neuronal activity augments Aβ production, which in turn leads to further neuronal damage (Palop and Mucke, 2010; Bero et al., 2011; Verret et al.,