Underpinnings Of Ab And Tau Phenotypes

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) is a progressive and fatal form of dementia, frequently seen in the elderly altering their cognition, thought process and behavior. AD is reported in about half of patients that have a dementia diagnosis; one study states that about 10.3% of the population over 65 years is affected by dementia with an increase to almost 50% over the age of 85. (Beattie, 2002) Alzheimer’s disease is not a normal part of the aging process in humans, but rather found in a group of diseases that affect the brain leading to a decline in mental and physical control. AD when diagnosed has a very slow and gradual course, initially affecting the individual’s short term memory. (Beattie, 2002)

More than five million are living with Alzheimer’s disease in the United States and the number is set to almost triple by the year 2050. It is common in the elderly and generally occurs in persons over 65 years of age, but early onset of Alzheimer’s has also been documented (“Alzheimer’s disease facts,” 2016, para. 1). It starts in the medial temporal area of the brain, usually in the hippocampus, and then spreads to other areas of the brain. Blows (2011) explains, “Alois Alzheimer was a German psychiatrist who in 1906 described a dementia with two specific changes found in the brain after death... these changes were the presence of extracellular plaques and intracellular neurofibrillary tangles and these became the hallmarks of this disease” (p. 286). Loss of neurons takes place and amyloid plaques form. This is due to build-up of non-functioning proteins and can be observed by imaging techniques (Radin, 2003, p. 41). There are many risk factors that increase the risk of Alzheimer’s disease. The greatest risk factor is family history, but other risk factors include diabetes, hypertension obesity, hyperlipidemia, smoking, depression, physical inactivity, low estrogen levels, and head trauma (Huether & McCance, 2014, p. 546). The actual cause of Alzheimer’s is unknown, but there are genes associated with it that make the disease heritable. What is clear is that

Type 2 diabetes is associated with poor sensitivity to insulin. This had led some some researchers to suggest that Alzheimer’s disease may in fact be another type of diabetes (Trivedi, Bijal, 2012).

Dementia is a syndrome which is progressive in nature, characterized by impairment of memory and loss of intellectual ability.1 Decreased level of Acetylcholine in the brain, neuro-inflammatory reaction, rise in the oxidative stress and hypercholesterolemia have been reported to play an important etiological role in the memory decline.2 Alzheimer’s Disease (AD) is the most common form of dementia which is a progressive and a neurodegenerative disease characterized by the presence of senile plaques rich in insoluble aggregates of β amyloid and neurofibrillary tangles in the brain. AD has been estimated to account for 50–60% of dementia cases in persons over 65 years of age worldwide.3 Alzheimer’s Disease International

Alzheimer’s disease (AD) is a slow-progressing neurodegenerative disease that has no cure and most often affects people over the age of sixty-five. Neurodegeneration is characterized by the loss of function in the central nervous system due to degeneration of neurons found mostly in the brain. The most recent data from the Center for Disease Control and Prevention shows that AD is the sixth-leading cause of death in the United States. The cause of Alzheimer’s is still not completely understood, but the current theory is that it appears to be genetic in which many genes are involved. AD is also the most common form of dementia and accounts for 60-80% of cases (Alzheimer’s Association 2016). Dementia is not a disease itself, but instead is characterized by a group of symptoms that is caused by brain disease or injury in which memory, personality, and reasoning skills are affected.

affected by numerous factors. A variety of genetic mutations can influence the severity and time course of AD. However, researchers acknowledge

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

Alzheimer’s disease is among the sixth top leading causes of death in the United States and even with an estimated 4.5 to 5.4 million suffering from Alzheimer’s disease (AD) not much is known about the causes. Only the symptoms are addressed. The main characteristics of AD are degeneration of the ability to remember, reason, communicate and with loss of motor skills and function (Piazza-Gardner, 2013). Cognitive function that is lost and is accompanied by other physiological conditions such as depression, anxiety, irritability, aggression and inappropriate behavior for a setting or location that occur in most AD suffers (Senie, 2014). AD was noted as abnormal clumps and a bundle of proteins in the brain which was discover in patients with

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear in their mid-60s (nih.gov). AD is a multifactorial and progressive neurodegenerative disease. Parts of AD, for example, increased oxidative state, amyloid plaque deposition, and neurofibrillary tangle of tau protein in the central cortex the limbic system of the brain, have been related with Alzheimer's disease. AD standouts amongst the most well-known and feared diseases burdening the elderly community. The disease was once thought to be a natural part of aging, is an extremely incapacitating type of mental dementia.

Following the ingestion of carbohydrates and proteins, insulin is released from pancreatic islet cells. Whilst the brain is not insulin dependent, the arcuate nucleus contains protein receptors that respond to insulin (as well as Leptin)[7]. As insulin inhibits NPY/AgRP-secreting neurons and activates POMC-releasing neurons, it reduces the appetite and as a result regulates body weight. This is backed up even further by scientific claims that insulin resistance is linked to obesity, and type II diabetes can be associated with a loss in insulin regulation[8].

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

While issues regarding concentration levels of Aβ, the types of Aβ and the mechanisms of its production remain poorly understood, some information has been found. For instance, the continuous overproduction of Aβ at dendrites or axons acts locally to reduce the number and plasticity of synapses (Parihar, 2010). Moreover, in mouse models for AD, the area of amyloid plaques is characterized by highly dysmorphic neurites and spine turnover causing a net loss of spines (Parihar, 2010). Such abnormalities in dendritic spines were found to develope before appearance of clinical symptoms in AD--likely due to cognitive reserve (Parihar, 2010). These characteristics could be caused by Aβ oligomers, which block long term potential (LTP) and directly induce long term depression (LTD), spinal loss and memory loss(Parihar, 2010). Likewise, in hippocampal culture, the soluble Aβ produced

The amyloid cascade hypothesis is the most widely accepted of the AD pathogenesis hypotheses. Its principle is that the accumulation of Aβ plays a major role in AD pathogenesis, and the disease is analyzed as a series of abnormalities in the process and secretion of the amyloid precursor protein (APP), where an inequality between production and clearance of amyloid β is the triggering event and the most important factor responsible for other abnormalities observed in AD (Hardy et al, 2002; Cummings et al, 2007). Amyloid β is a peptide with high resistance to proteolytic degradation. It consists of 37–43 amino acids with different isoforms (Deane et al, 2009). Aβ is the result of sequential cleavage of the amyloid precursor protein (APP), generating