English 302-N07
Narration Revision
Alzheimer’s Disease is a degenerative disease of the brain which causes a person to lose all ability of memory, reasoning, and conversation. It is named after Alois Alzheimer who published results to post-mortem neuropathalogical observations in 1907 on a 56-year old demented patient who showed the classic symptoms of the disease. This is a disease in dementia which is a mental disorders of adults (Whalley 111) and is a disease of old age and it usually starts with people around the age of 65 (Strange 201). Alzheimer's Disease is a disease in which neurons of the brain are killed and the person with this disease suffers sporadic periods of memory loss (Castegna). There are many social, psychological, physical, behavioral, mental, chemical, and emotional changes involved in this disease. Behaviorally, a person’s mood can seem to have added aggression, depression, wandering, aphasia (loss of language), apraxia (impairment of purposeful movements), and agnosia (loss of recognition of objects). There are also physical changes of the brain such as shrinkage of the gyri around the frontal and temporal lobes, loss of white matter, loss of pyramidal neurons in the frontal, parietal, and temporal lobes, and the change in breadth and thickness of the cerebral cortex (204). All these changes are parallel in concluding the degree of how far along Alzheimer’s Disease really is. The chemical changes involved are numerous and are the underlying reasons of why all the other physical, behavioral, and mental changes happen.
The brain undergoes various reductions and changes in its chemical activity. For instance, there is a cholinergic marker enzyme, called choline acetyltransferase, which is responsible for acetylcholine synthesis (208). There is also a reduction in 5-hydroxytryptamine, which contributes to the psychiatric problems that are often symptoms of Alzheimer’s (225), and noradrenaline neurons are observed in the cerebral cortex (Strange 209). The levels somatostatin, which is the hormone responsible for inhibiting the release of the growth hormone and the thyroid-stimulating hormone that is comprised of two peptides and is secreted by the hypothalamus, are reduced. Glutamate is a fast excitatory neurotransmitter of the cortical pyramidal neurons and is stored at the vesicles at the synapse of the neuron. It is involved in the cognitive functions of the brain such as learning and memory. Its levels are also reduced at the synapses of the neurons which cause a lessening of a person’s ability to retain cognitive function. Asymmetrical reduction in glucose metabolism happens very early in the disease and there is a correlation between neural degeneration and reduced glucose metabolism. Associated defective tissue metabolism indicates a defect in oxidative phosphorylation and energy production which also could be due to malfunctions of the mitochondrial electron transport chain (Strange 210). It is being researched and is found to believe that the nitration of tyrosine, which is one of the 20 amino acids used to synthesize protein, causes an event that leads to degenerative diseases like Alzheimer’s. It has also been found that in a brain with the disease, there are more nitrated proteins than in a regular brain. The simple reaction of NO (Nitrogen Oxide) and O2 (Oxygen) can form ONOO- (Peroxynitrate) which generates molecules that can nitrate proteins. There is still research going on about these statements but it is also led to believe that the nitration and oxidative protein can lead to neural death, which is where Alzheimer’s symptoms start (Castegna). The amyloid ß-protein could have been a precursor that was found in the genes that might have helped in finding out what causes Alzheimer’s. Amyloid protein accumulation in aging organs can make pleated sheets called ß-pleated protein and these fibrils accumulate in all Alzheimer’s patients (Whalley 129). The structure of the protein is that it involves a chain of amino acids linked by peptide bonds and through reverse genetics, scientists have found the amyloid precursor protein on Chromosome 21 and due to its extra copy. Beta-secretase plays an important role in development of the protein clumps of ß-amyloid that form in the disease and damage mental function, so as researchers were looking for compounds that might inactivate it a recent report stated that “scientists in Germany, Belgium and the United States report…that beta-secretase is also involved in myelination, the formation of a protective covering for nerve cells early in life. Interfering with that activity could cause lifelong nerve damage, the researchers speculated” (Alzheimer’s).
Although there is no treatment available to stop the inevitable progress of the disease, several pharmacological actions are being tried in order to at least slow down the degeneration of the brain such as altering neurotransmitters, oxygen usage, and blood flow to the brain. Scientists have also used treatment with L-DOPA, which is also known as levodopa, to increase the dopamine deficit that is likewise used in treating patients with Parkinson’s disease. The deficit of cholinergic enzymes can be treated by using choline and lecithin to increase acetylcholine levels, using anticholinesterases such as tetrahydroaminoacridine, and using muscaramic cholinergic agonist such as bethanechol that can mimic the action of acetylcholine (Strange 222). Many treatments are still being researched and many are yet in the process of being tested, but whatever treatment comes out, it will only be due to a solid understanding of how the chemistry of the brain works in the start and duration of Alzheimer’s.
“Alzheimer’s Study Raises Warning Flag.” Medline Plus. Healthday. 21 September
2006. Accessed 24 September 2006.
Castegna, A. "Proteomic Identification of Nitrated Proteins in Alzheimer's Disease
Brain." PubMed (2003): June 2003
Strange, Philip G. Brain Biochemistry and Brain Disorders. Oxford University Press: New York, 1992.
Whalley, Lawrence. The Aging Brain. Columbia University Press: New York, 2001.