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Alzheimer's Disease: A Neural Pathway Disjunction

Madina G.'s picture

Alzheimer’s disease affects an estimated 24 million people worldwide (8) and was the seventh leading cause of death in America in 2007 (1). It is often recognized based on the symptoms of dementia, one in which loss of memory, motor skills, language ability and attention span are demonstrated in an individual who suffers from the illness, however Alzheimer’s has a deeper root in the nervous system that requires evaluation to help rectify the damage that it can cause. It is a severe disturbance in the neurological pathway between input and output signal transducers. The connection between an input and output transducer is the very essence of how the nervous system functions. Given that all action potentials throughout the body are generated identically, it is solely this connection that helps gives rise to some of the basic everyday functions we are able to perform. A disturbance in any of these pathways would result in drastic alterations of the output signal emitted, and can subsequently have dire effects on basic bodily functions. To evaluate the significance of proper connection between input and output devices within the nervous system, let’s look more closely at the mechanism by which Alzheimer’s disease develops.

Currently, there are three hypotheses that account for the development of Alzheimer’s disease. The beta-amyloid hypothesis proposes that Alzheimer’s stems from an accumulation of beta-amyloid. This is a protein fragment excised from the polypeptide, amyloid precursor protein (APP) which is produced in the brain and suspected to have functional significance in regulation of neural plasticity(2). APP is typically degenerated by enzymes and eliminated, although in some instances it can degrade to form insoluble beta-amyloid segments that clump after they undergo fragmentation (3). Small fibers are emitted from these fragments and adhere together to form a hard, insoluble product called beta-amyloid plaque (3). This is a prime perpetrator in the damaging of ion channels embedded in the membrane of neurons. Ion channels allow for the passage of sodium, potassium and calcium ions which are factors required for the firing of signals across a synapse and when damaged, the result is failed signal transduction (3).

Another hypothesis suggests that Alzheimer’s is a result of decreased levels of the neurotransmitter acetylcholine. The role of acetylcholine is vital, as it is responsible for facilitating signal transduction over synapses in several neurons at once. It is a particularly crucial chemical messenger of the brain for its role in learning and memory, two skills found that suffer the most declines in Alzheimer’s disease (3).

The third hypothesis proposes that tau protein malfunctioning is the core instigator of Alzheimer’s disease. Tau proteins function to stabilize tubilin filaments found in microtubules, the main constituent of the neuron skeleton as well as the channel system that carries nutrients essential for cell survival (3). Tau proteins can undergo entanglement if it becomes hyperphosphorylated into an insoluble form, and can accumulate producing masses of neurofibrillary tangles (3). When these tangles are formed, the tau protein can no longer perform its intended function and as a result the cells collapse. Loss of memory and learning skills associated with dementia arise from the death of these neurons.

Each of the proposed hypotheses of the mechanism by which Alzheimer’s disease progresses share a common thread that explains the reason for which the effects of Alzheimer’s are so severe: a profound disturbance of the pathway connecting the input and the output devices within the nervous system. As all action potentials that are generated within the nervous system are the same, that is to say that they are not specific to any particular function, the output response to the action potential relies completely on the wiring mechanism of the nervous system. The correct functioning of a given pathway that connects the input and output devices is particularly crucial. Just as a paraplegic would claim to not feel anything in their foot because a stimulus applied to their foot cannot transmit a signal to the brain (due to the severing of a nerve that would otherwise allow this physical connection) (4), similarly a patient of Alzheimer’s disease claims they cannot remember because of a break in the pathway of signal transduction for memory.

Treatments for Alzheimer’s disease have been developed to ease some of the symptoms, however no cure has been found to reverse the grave effects of the mass neuron destruction that occurs. Treatments include acetylcholinerase inhibitors which prevent the enzyme acetylcholinerase from breaking down acetylcholine, thereby increasing the levels of the neurotransmitter needed especially for memory and learning (5). In addition, some compounds have been designed to decrease the production of beta-amyloids whose aggregation is proven to be poisonous to healthy, functional neurons. Therapeutic measures can also be taken such as reminiscent therapy to help retrieve memory (9), creating calm environments to reduce agitation in the patient as well as keeping a regular schedule of activities for the patient with little divergence to establish regularity and familiarity between the patient and their surroundings (6). Deep Brain Stimulation techniques are opening eyes to a possible complete retrieval of memory, but this technique still requires further testing (7).

Although current treatments are unable to fully reconstruct the pathway of input and output transducers, the unraveling of possible mechanisms that outline the development of Alzheimer’s disease illuminates a greater understanding of what the disease is: a severance in the cabling of the nervous system at the synaptic level, in the region of the brain that governs skills in memory, language and attention. Frustration that arises from inability to recollect, language impairment and other dysfunctions is expressed in behavioral changes such as increased agitation and depression. But the greatest consequence of Alzheimer’s is death as a result of the destruction of so many brain cells that participate in the regulation of basic bodily functions. The devastating effects of Alzheimer’s is a marker of the powerful and yet vulnerable properties that the connection pathways within the nervous system possess.

1) Alzheimer’s Association,, Accessed 22 Feb. 2008
2) National Center for Biotechnology Information,, Accessed 22 Feb. 2008
3) The Alzheimer’s Brain,, Accessed 22 Feb. 2008
4) Class Notes from Dr. Paul Grobstein on 2/7/08
5) American Academy of Family Physicians,, Accessed 22 Feb. 2008
6) Fisher Center for Alzheimer’s Research Foundation,, Accessed 22 Feb. 2008
7) Boston Globe News Article,, Accessed 22 Feb. 2008
8) The Lancet,
9) University of Pennsylvania Health System Alzheimer’s Disease Center,


Paul Grobstein's picture

Alzheimer's: interruption of cables?

"a patient of Alzheimer's disease claims they cannot remember because of a break in the pathway of signal transduction for memory."

That's a very interesting extension of our notion of the nervous system consisting of boxes linked by cables. What kinds of additional observations would or would not be consistent with this? What kinds of new questions does it raise? Is Alzheimer's a special case or would you make a similar argument about other variations in brain function?