Alzheimer's Disease and It's Secondary Disorders that Impair Movement.




3-s2.0-B978008045046900509X-gr1.jpg

Introduction: Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder. It can be diagnosed at any time during life, but is most common in the elderly. It is characterized by the presence of abnormal protein aggregates in the neurons and the extracellular space of the central nervous system. There are shingles, which are lesions composed of neurofibrillary tangles and senile plaque that get in the way of pathways of neural signals. This causes things to be slowed down in specific activities of daily living and cause a major deficit in memory. Large filaments of a small peptide, amyloid β-protein (Aβ) are what compose the lesions. Along with many memory deficits, there are also common movement disorders that can come along with having AD. Since there is significant trouble with axonal transport from one neuron to the next, research has shown that there is still a lot more to be researched, but there are traces of Agnosiaa and Ideomotor Apraxia associated with AD. The main reasoning behind all of this is because of the disrupted pathways of axonal-neural transport.


Figure 1. Shows a brain with AD (left) compared to the brain of an individual without AD (right).






Axon-Neural Transport:
Axonal transport is essential for maintaining the structure and function of nerve cells. Deficits in axonal transport have been proven to be a major reason why there are movement deficits in Alzheimer's disease. The reason why there are so many axonal transport problems is because of the AD-related proteins that regulate the transport of axons, and make it abnormal. Using mouse models, a recent study has demonstrated that the axonal transport deficit occurs early in the course of AD. The study showed that reduced axonal transport leads to increased amyloid β production and deposition, which only continues to decrease accurate axonal transport. This is the explanation for the impairments of movement and memory to start, and can only continue to get worse when more amyloid β gets produced in the extracellular fluid of the brain. Overall, axonal transport deficits can be sought as the main reason in the pathogenesis of Alzheimer's.
1-s2.0-S1471491405001644-gr1.jpg
Within the two figures above, the figure on top is a model of axonal transport in a healthy person. In healthy axonal transport, there is a bidirectional transport pathway. In these pathways, microtubules are polarized tracks along which motor proteins travel in the neuron. Anterograde transport, is controlled by positively charged directed transport and the motor protein kinesin. In the other direction, retrograde transport is controlled by negative charged directed transport and the motor protein dynein. Other proteins such as Tau protein are anterogradely, in other words, positively charged and transported to their destination in axons. AβPP is also anterogradely transported to synaptic vesicles in the post synaptic cleft of the receiving neuron.

The bottom figure shows the model of axonal transport in a person with Alzheimer's Disease. In neurons of a person with AD, axonal blockage or other defects such as reduced microtubule density causes reduced axonal transport. From before, reduced axonal transport leads to the accumulation of the protein AβPP. This protein contains vesicles in axonal and somatodendritic compartments, which will eventually call upon the β-cleavage of AβPP to increase intracellular Aβ levels and plaque deposition. In a healthy person, the generation and release of Aβ might activate a negative signal, which phosphorylates and activates other proteins, which gets a retrograde, or a negatively charged transport, back to the cell body to build repair signals that were damaged, and kill
off the protein causing the blockage. This security system that a normal brain has access too, are impaired in the brain with Alzheimer's.






gend_01_img0014.jpg

Ideomotor Apraxia & Alzheimer's
Ideomotor Apraxia isadisorder which occurs in thesecond stage of AD, whichis the stage of confusion, that starts anywhere between three and six years of being diagnosed withAD. It is associated with damage to thecortex of the brain. These disease is a disturbance of voluntary movement because of adisconnection between the idea of a movement and its execution. People with ideomotor apraxia can still perform most automatic movements.However, they cannot perform such movements upon request. They also have difficulty copying movements, using tools, or making gestures. It means that people with this secondary disorder in AD require one and two step skills. This damage to the parietal cortex is further associated with deficits neuronal axonal transport in the premotor/parietal cortex. This is the area in the brain responsible for planning. That is where the confusion comes in when an individual with AD knows they need to complete a task, but does not know how to carryit out or forgets how to.

Video Showing Effects Apraxia

Agnosia & Alzheimer's
agnosia4.jpg

AD affects the brain's ability to understand and recognize visual input. Agnosia can result from this which refers to the loss of ability to recognize objects, people, sounds, shapes, or smells. This also starts in the second stage of AD which is confusion. There are three types of this disease that any patient with AD can enquire: visual agnosia, auditory agnosia, and tactile agnosia. For example, a person with agnosia might attempt to use a fork instead of a spoon, a shoe instead of a cup, or a knife instead of a pencil. With regard to people with AD, this might involve failing to recognise who people are, as a result of the brain not working out the identity of a person, on the basis of the information supplied by the eyes in visual agnoisa. This damage to the brain is further associated with deficits neuronal axonal transport across area associated with visual processing and sensorimotor areas of the brain.

Video Showing Effects of Agnoisa




Conclusion:


The main cause and increasing issues and deficits that come with Alzheimer's Disease is a result of a deficit in axon-neuronal transport. This causes lesions in the brain composed of proteins that cause blockage and shingles filled with plaque within the pathway of axons and extracellular space of the brain. Reduced axon transport means that more of the amyloid β-protein (Aβ) is produced, which only results in more impaired transport. These deficits in axonal transport can cause secondary disorders that cause difficulties in voluntary acts and movement. Two examples of this is Apraxia, which is a disorder that disrupts automatic movements, and Agnosia which causes deficits in being able to see, hear, and touch. There is no treatment for Alzheimer's and therefore, not much can be done to cure the secondary diseases that come along with it that impair movement.



Glossary:

Alzheimer’s disease (AD): Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder. It can be diagnosed at any time during life, but is most common in the elderly. It is characterized by the presence of abnormal protein aggregates in the neurons and the extracellular space of the central nervous system.

Axon-Neural Transport: Axonal transport is essential for maintaining the structure and function of nerve cells. It is what neurotransmitters go through to get signals across to different cells in nervous system.

Ideomotor Apraxia: It is associated with damage to the parietal cortex of the brain. These disease is a disturbance of voluntary movement because of a disconnection between the idea of a movement and its execution.

Agnosia: The loss of ability to recognize objects, people, sounds, shapes or smells, when the required sense is not defective.

Premotor Cortex: The part of the brain associated with planning movements

Axon: The part of a neuron that transmits received signals to the axon terminal where the signal than gets transmitted to the dendrites of the next neuron.


Quiz:

T or F


1. People encounter Alzheimer's disease because of lesions associated specifically in the cerebellum of the brain.

2. Axon-neural transport has been found to be one of the leading causes of Alzheimer's.

3. Agnoisa results in problems with balance and coordination of movement

4. Signs of Apraxia occur in the 2nd stage of AD, which is the stage of confusion.

5.The protein associated with lesions in the axonal pathway is amyloid β-protein (Aβ).

6. Apraxia is a result of damage due to the temporal lobe



Short Answer:

1. What causes problems in axon-neuron transport of a person with AD?

2. Name the three types of Agnoisa and the stage of AD that is occurs in.

3. Name the symptoms of Apraxia and how axon-neuron transport plays a role in the deficits of it and AD.


Answers to T/F: 1=F 2=T 3=F 4=T 5=T 6=F


Suggested Readings & Websites:

Slowly Progressive Apraxia in Alzheimer's Disease

More on Alzheimer's

More on Agnoisa


References:

Alzheimer's Europe. 2009. Main Characteristics of Alzheimer's.Alzheimer's Europe.
http://www.alzheimer-europe.org/EN/Dementia/Alzheimer-s-disease/Main-characteristics-of-Alzheimer-s-disease/Apraxia-Aphasia-Agnosia#fragment-2

Zhu, Xiongwei., Moreira, Paula I., Smith, Mark A., Perry, George P.2012. Alzheimer's disease: An intracellular movement disorder?. Science Direct. Case Western Reserve University. Cleveland, OH. http://www.sciencedirect.com/science/article/pii/S1471491405001644

Cairns, N.J. 2009. Alzheimer's Disease: Neurodegeneration. Science Direct. Washington University School of Medicine, St. Louis, MO.
http://www.sciencedirect.com/science/article/pii/B978008045046900509X

Carone, Dominic. MD. 2012. Alzheimer's Disease. MedFriendly. http://www.medfriendly.com/about_medfriendly.html

Lelani, Doty, PhD. 1990. Stages of Alzheimer's Disease. University of Florida Memory Disorder Clinic. Gainesville FL. http://alzonline.phhp.ufl.edu/en/reading/AlzStagesHdout.pdf


Zadikoff, C., Lang, AE. 2005. Apraxia in Movement Disorders. US National Library of Medicine National Institutes of Health. Bethesda, MD.
http://www.ncbi.nlm.nih.gov/pubmed/15930045

Dementia Guide. 2012. About Dementia: Alzheimer's Disease- Agnoisa. Dementia.
http://www.dementiaguide.com/aboutdementia/alzheimers/agnosia/



Videos:
http://www.youtube.com/watch?v=gewP1T7GYcc & http://www.youtube.com/watch?v=dG8JGg-d2Pk