Alzheimer's Disease

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                                                                                                                        Rama Kirloskar

                                                Alzheimer’s disease

Alzheimer’s disease (AD) is a type of dementia that is very common in older people. The main symptom that is characteristic of Alzheimer’s disease is loss of memory. Since memory declines with age, differentiating between forgetfulness due to age and loss of memory due to AD can be difficult in diagnosing, which is why the category of “mild cognitive impairment” has been created. People suffering from mild AD have symptoms that begin with a gradual loss in memory such as forgetting that they had a particular conversation, not being able to find words to express themselves, getting lost in familiar neighborhoods, repeating questions and changes in behavior. At a moderate stage, AD damages areas of the brain that control language, reasoning, and sensory processing. At this stage there is an increase in forgetfulness, confusion, the patient may have trouble recognizing family and friends, is unable to learn, and has trouble performing daily activities involving many steps such as getting dressed and has dramatic personality changes. At a very advanced stage, the patient is unable to communicate and is completely bed-ridden and dependent on the family.

            The causes of Alzheimer’s disease are still not fully understood. However, the brain of a patient suffering from AD has many clumps called amyloid plaques and tangles called neurofibrillary tangles. These tangles which are basically large inclusions in neurons develop in a region of the brain called the entorhinal cortex. As these tangles increase in number, the neurons in the brain begin to function more and more inefficiently. Eventually, the neurons are unable to communicate with each other and die. This damaging process spreads to neighboring parts of the brain, such as the hippocampus, which is responsible for memory formation. As neurons in different parts of the brain begin to die, the brain tissue in the affected regions undergo a significant decrease in size.

            We know that a lot of neurodegenerative diseases stem from the over accumulation of proteins in the nervous system. In AD, these are Aβ peptides, apolipoprotein E, the protein tau and α-synuclein. The Aβ peptide is made in the brain and other parts of the body and is released from the amyloid precursor protein after cleavage by enzymes such as β-secretase and γ-secretase. Aβ is usually removed from the brain by clearance mechanisms, but if its concentration increases due to overproduction or deficient clearance, the Aβ self-aggregates forming oligomers and amyloid plaques, which are basically, the “clumps” I previously mentioned. The protein Tau is a microtubule-associated protein and α-synuclein is a presynaptic protein. Both Tau and α-synuclein are capable of self-aggregating into oligomers and forming neurofibrillary tangles and Lewy bodies. Scientists think that the lipid carrier, apolipoprotein E, may contribute to the over accumulation of Tau and Aβ. Over accumulation of proteins causes impairment in neural activity by blocking synapses between neurons in regions of the brain controlling language, memory, learning and other cognitive processes. It is also thought that AD affects older people due to decreased rate of clearance mechanisms in the brain.

Some Thoughts on Alzheimer’s disease:

Trying to explain the pattern of behavior followed by Alzheimer’s patients:

A computer stores information in the form of a binary code. A binary code consists of only zeros and ones and different combinations of zeros and ones will have different meanings for the computer. The neural cells in our brain are able to make millions of connections with each other. When we learn, information is stored in the form of a neural connection, and just like a computer, different combinations of connections have different meanings for us. Thus, the act of dancing will have a different combination of connections, compared to the act of playing basketball. We must note that both activities share basic common actions like the movement of limbs.

So, if we imagine that the set [0,1] is the set for the binary code in a computer, then all binary codes that use different combinations of zeros and ones will be the subsets of the set [0,1]. In the same manner, all movement learnt during childhood can be the set [all movement] and every subsequent skill learnt that uses movement will be a subset of the set [all movement]. Each of these subsets will in turn become sets for other subsets. This can also be shown using a branching pattern as we go from a very general activity to a very specialized activity. The main point is that all subsequent learning is based on the foundation of basic learning that one attains during childhood.

            The phenomenon taking place in AD is the destruction of the nerve cell which is equivalent to the destruction of the set [0, 1] of the binary code. Destruction of the main set leads to destruction of all following subsets. As a result, the individual cannot perform very basic activities like talking, getting dressed etc.

Trying to explain different personality changes in people with Alzheimer’s disease:

People with Alzheimer’s disease suffer from dramatic changes in personality. I feel that personality is the result of the number and location of connections in our brain. People develop different personalities due to the formation of different neural connections, as they have different experiences, perform different activities, live in different environments and study different subjects. Since people are wired differently, I feel that people will have a different personality change as they will lose a different part of their circuitry at a given time.

Thoughts on finding a possible cure:

I know that during the early development of the mammalian heart in the embryo, the heart begins to function, pumping blood through its valves, even when it is not fully formed. Thus if an organ has the capacity to function while it is being created, then by the same logic, the brain could be made to function, while it is being destroyed, as in both cases the organs are incomplete. For Alzheimer’s disease, maybe we could find a way to keep all the neural networks stimulated all the time, so that even clumps and tangles formed in the brain will not affect the neural synapses considerably. Performing an activity repeatedly strengthens the neural connections and so people will not forget as fast. If performing an activity repeatedly, ensures that we do not forget it easily, then I feel that the first connections that an Alzheimer’s patient will lose are those that correspond to activities that he does not perform on a daily basis. This will be true for memory also. In order to make sure Alzheimer’s patients do not deteriorate as fast in cognitive processes, maybe we could develop a software or a video game that makes them exercise areas of the brain associated with cognition.

Sources Cited:

1)    http://www.nia.nih.gov/Alzheimers/Publications/adfact.htm

2)    http://www.aarp.org/health/brain/works/what_is_learning.html

3)    http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html

4)     Lennart Mucke (2009) Alzheimer’s disease. Nature 2009