First the facts
As of today 5.4 million Americans are living with Alzheimer’s disease (AD). There are several forms of dementia with Alzheimer’s being accountable of 50-80% of dementia cases. It is the 6th leading cause of death in the United States and since the year 2000 the death toll has risen by 66%. It is evident that the numbers of Alzheimer’s cases is rising with an expected 16 million Alzheimer’s cases by 2050. As alarming as these numbers are, what is most troublesome is that at this time there is no cure, ability to prevent or considerably slow down the progression of this insidious disease.
What is Alzheimer’s?
It is a neurodegenerative disease that is slow progressing and affects normal brain function that ultimately leads to death. Diagnosis of the disease can be categorized into stages dependent on cognitive function. Diagnosis is carried out by a medical assessment that evaluates a patient’s medical history, mental capabilities, physical and neurological exams, and other tests that are utilized to eliminate other potential disease that can be contributing to cognitive decline.
Histopathological hallmarks of Alzheimer’s disease are plaques and neurofibrillary tangles. How these hallmarks arise can offer insight into the pathogenesis of Alzheimer’s disease, but understanding their presence and how they disrupt the neural network can provide targets for drug therapies, which are currently being researched and developed.
· A major component in plaque formation is a protein by the name of amyloid. This protein is cleaved and beta-amyloid fragments become sticky and cluster together to form plaques. The formation of these plaques displaces the neuronal network leading to disruption in neuronal signaling. Furthermore, the cleaved beta amyloid fragments can form oligomers (several of the fragment stuck together but not forming a distinct plaque) that can migrate into synapses (site where signal is communicated between two neurons) and hinder signaling.
· Neurofibrillary tangles are formed when a tau protein of a neuron become tangled which leads to the lost of productive signaling down the neuron due to the tangling. The tau protein is highly present at the axon, which is critical in conducting a signal down the neuron and onto the next connecting neuron(s).
The presence of tangles and plagues lead to a disruption of neuronal signaling, which due to the lost of the ability to signal leads to neuron and tissue death. The brain has approximately 100 billion neurons making 100 trillion connections via synapses, which is mostly likely why we see a lengthy progression in the onset of Alzheimer’s. However, the presence of plaques and tangles develop in specific regions of the brain and then slowly progresses to other areas. As more neurons and tissue are lost the brain begins to shrink and decline in cognitive and becomes more severe; we will initially witness in Alzheimer’s patients difficulties in memory recall; however, as the disease progresses and more areas of the brain are affected we see adverse changes in memory capabilities, behavior, movement and body functions. There are 7 distinct stages that categorize the symptoms exhibited by someone suffering Alzheimer’s. The stages are defined by the decline in cognitive function and ability to maintain movement and body functions. The progression and type of symptoms an individual will experience varies.
How may inflammation play a role in Alzheimer’s?
Even though at first glance it looks like our focus should be solely on neurons, studies have revealed another component to be considered are glial cells and inflammation. It has been hypothesized that glial cells become activated upon injury and have the ability to induce pro-inflammatory cytokines. The continue activation of these cells could lead to an extended and increased expression of pro-inflammatory cytokines/chemokines inducing low grade inflammation. Extensive research has been conducted to evaluate the effects of the increase levels of pro-inflammatory cytokines/chemokines, which have shown to have correlation to cognitive decline and may offer insight into the pathogenesis to AD. Glial cells can also play a role in synthesizing the amyloid precursor protein, which when cleaved into fragment has been shown to have the ability to form plaques and oligomers that disrupt signaling, but it can also induce the expression of pro-inflammatory cytokines, for example Il-6. In addition to the inflammation that is induced by the cytokines/chemokines they also possess the ability to induce signaling cascades that contribute to plaque and tangle formation, which are hallmarks to AD. Neuroinflammation is complex and its contribution to understating AD is a work in progress; however, it is a hallmark of AD and its components have potential to be a useful tool to target for treatment, prevention, diagnosis and insight to the pathology of AD.
Resources:
http://www.alz.org/
Rojo, et. al Neuroinflammation: Implications for the Pathogenesis and Molecular
Diagnosis of Alzheimer’s Disease. Archives of Medical Research 39 (2008) 1e16
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