This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison Spring 2009
Alzheimer's Traits and Prevalence
Alzheimer's Disease (AD) is a progressive, neuro-degenerative disorder mostly commonly found in elderly populations. As the most common form of dementia among the elderly(1), Alzheimer's is a major contributor to the loss of self-sufficiency for a large population. Dementia is a blanket term for a category of disorders of which the characteristic symptom is “serious problems with two or more brain functions, such as memory and language.”(2) Of course, the characteristic symptom of Alzheimer’s is memory loss, often to the point where the affected individual suffers from memory loss so severe they do not recognize or remember members of his/her own family.(3) Alzheimer’s Disease (AD) is a all to common, with recent estimates projecting between 2.5 and 4.5 million Americans suffering from AD.(1) Simply put, “AD is an irreversible, progressive brain disease characterized by the development of amyloid plaques and neurofibrillary tangles, the loss of connections between nerve cells in the brain, and the death of these nerve cells.”(4)
What is AD?
Click on this YouTube video to hear a brief description of AD and the number of people it effects.
What does AD do to the brain?
Fig 2. As you can see, AD truly is a neuro-degenerative disorder. This coronal view of the brain shows a few of the characteristic results of AD: cerebral cortex atrophy (which effects planning, thought, and executive function among other things), decreased hippocampus volume (an area vital for memory formation and storage), and an increase in the size of the ventricles (the areas of the brain where fluid is stored). This picture and information comes from the Alzheimer's Association.(7)
So how does SORL1 play into all this?
SORL1 is able to interact with both amyloid precursor protein (APP) and VPS 35 to direct whether APP enters the retromer recycling pathway or instead enters the late endosomal pathway. Scientists have demonstrated that over expression of SORL1 leads to an increase in the percentage of APP entering the recycling pathway and therefore a decrease in amyloid b peptide (Ab) production. Likewise, the silencing of SORL1 leads to an increase in the percentage of APP that enters the late endosomal pathway (Rogaeva, 2007). Taken together, this data indicates that SORL1 plays an important role in the determination of the path APP takes. This is important because the late endosomal pathway leads towards the accumulation of Ab peptide, which has previously been shown to play a substantial role in the pathology of AD (Mattson, 2004).
SORL1 Acts as a Switch
Fig 1. The APP processing pathway illustrates the important role SORL1 plays as a switch in this process. In Alzheimer's Disease there is a decrease in the amount of SORL1 present, which directs APP toward the BACE1 arm which leads to an increase in the amount of Ab (a direct precursor of the characteristic Alzheimer’s Plaques) that is formed. This figure is taken from Rogaeva, E., et. al. (2007) The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nature Genetics, 39 (2).
Who's Looking at this Site?
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References
1National Institute on Aging Alzheimer's Disease Fact Sheet
2MedlinePlus: Dementia
3MedlinePlus: Alzheimer's Disease
4National Institue on Aging: Alzheimer's Disease Genetics Fact Sheet
5Rogaeva, E., et. al. (2007) The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nature Genetics, 39 (2).
6Mattson, M.P. (2004). Pathways towards and away from Alzheimer’s disease. Nature, 430 (5).
7Alzheimer's Association
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Email: [email protected]
Last Updated 5/13/09
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