Etiology and Pathogenesis of Alzheimer Disease

        The exact cause is unknown. Some of the causes that have been made alternative hypothesis is metal intoxication, impaired immune function, viral infections, air pollution / industrial, trauma, neurotransmitters, deficit filament formation cells, heriditer pre-disposition. Alzheimer's disease pathology abnormalities basics consisted of neuronal degeneration, the specific area of brain tissue death resulting in impaired cognitive function with progressive loss memory.

Deficiency of growth factors or amino acids, may play a role in the selective death of neurons. The possibility of such cells undergo degeneration caused by an increase in intracellular calcium, failure of energy metabolism, the formation of free radicals or the presence of abnormal protein production of non-specific.
Alzheimer's disease is a genetic disease, but some studies have shown that the role of genetic factors, but some studies have shown that the role of non-genetic factors (environment) is also involved, in which environmental factors trigger just as genetic factors.

Pathogenesis of Alzheimer's disease are:

1. Genetic Factors
      Some researchers revealed 50% prevalence of Alzheimer's cases is autosomal dominant inherited through genes. The first line of descent individuals in families at risk of suffering from Alzheimer dementia 6 times larger than the normal control group. DNA genetic screening in patients with familial early-onset Alzheimer's disease there is a locus on chromosome 21 abnormalities in the proximal region of the long arm, whereas in late onset familial abnormalities found locus on chromosome 19.
      Similarly, in patients with Down syndrome whose chromosome 21 gene abnormalities, after 40 years there are neurofibrillary tangles (NFT), and decreased senile  plaque. Cholinergic markers depicting the brain tissue abnormalities in patients with Alzheimer's histopathology.
      The results of the study of Alzheimer's disease, the twins, showed 40-50% are monozygote, and 50% were dizygote. This situation supports that genetic factors play a role in Alzheimer's disease. In sporadic non-familial (50-70%), some sufferers found abnormalities of chromosome 6 loci, this situation presents the possibility that environmental factors determine the genetic expression in Alzheimer's disease.

2. Infection Factors
     There is a hypothesis shows the infecting virus in patients with Alzheimer's families conducted immuno blot analysis, its found the presence of antibodies reactive. Infectious virus causes infection in the central nervous system that is slow, chronic and remission. Some infectious diseases such as Creutzfeldt-Jacob disease, allegedly associated with Alzheimer's disease.

Hypothesis has some similarities include:
a. Clinical manifestations of the same
b. The absence of a specific immune response
c. Presence of amyloid plaques in the central nervous
d. Onset myoclonus
e. spongioform appearance

3. Environmental factors
       Ekmann (1988), said that environmental factors may also play a role in the pathogenesis of Alzheimer's disease. Environmental factors, among others, aluminum, silicon, mercury, zinc. Aluminum is a neurotoxic potential in the central nervous system were found neurofibrillary tangles (NFT) and senile plaque (spinal).
The foregoing shall not be explained with certainty, whether the presence of aluminum is the primary cause of degeneration neurosal or something that overlap. In Alzheimer's patients, also found objec imbalance mercury, nitrogen, phosphorus, sodium, the pathogenesis is unclear.
      There are allegations that the amino acid glutamate receptors would cause depolarization via N-Methy D-aspartate that will go into intracellular calcium (liquid-influx) and cause damage to cellular energy metabolism resulting in damage and death of neurons.

4. Immunological Factors
     Behan and Felman (1970) reported 60% of patients suffering from Alzheimer obtained serum protein abnormalities such as decreased albumin and increased alpha protein, anti-trypsin alphamarcoglobuline and haptoglobuline.
     Heyman (1984), reported a significant relationship exists and the increase of people with Alzheimer's disease with thyroid patients. Thyroid Hashimoto is a chronic inflammatory disease which often found in young women because of the role of immunity factor.

5. Trauma Factors
     Several studies have shown an association with Alzheimer's disease with head trauma. It is associated with boxers with dementia pugilistic, where the autopsy found a lot of neurofibrillary tangles.

6. Neurotransmitter Factors
Neurotransmitter changes in the brain tissue of Alzheimer's patients have a very important role, such as:
a. Acetylcholine
     Barties et al (1982) conducted a study of the specific activity of neurotransmitters in a way stereotactic biopsy and brain tissue autopsy in Alzheimer's patients, found decreased activity of acetylcholine transferase, acetylcholine esterase and choline transport and decreased the biosynthesis of acetylcholine.
The existence of presynaptic and postsynaptic cholinergic deficit is symmetrical on frontal cortex, superior temporallis, basal nucleus, the hippocampus. Abnormalities neurottansmiter acethylcholine is a disorder which always there than neurottansmiter types other than Alzheimer's disease, in which the brain tissue / biopsy always got lost cholinergik Marker.
In the study by administering scopolamine in normal people, would lead to reduced or loss of memory. This strongly supports the cholinergic hypothesis of Alzheimer's disease pathogenesis.
b. Noradrenaline
     Levels of norepinephrine and dopamine metabolism in brain tissue obtained decreased Alzheimer's patients. The loss of the dorsal locus ceruleus neurons which is a major noradrenaline in the cerebral cortex, correlated with cortical noradrenergic deficits. Bowen et al (1988), reported the results of the biopsy and autopsy brain tissue of Alzheimer's patients showed a deficit of noradrenaline at the presynaptic neocortex. Palmer et al (1987), Reinikanen (1988), reported a decreased concentration of noradrenaline in both post and ante-mortem Alzheimer's sufferers.
c. Dopamine
     Sparks et al (1988), measuring the activity of the hypothalamus region neurottansmiter, where no disturbance changes in dopamine activity in patients with Alzheimer's. These results are still controversial, probably due to the hypothalamus region of the pieces histopathology loyal different studies.
d. Serotonin
        It was found decreased levels of serotonin and the metabolism of 5-indolacetil hidroxi acid on biopsy of the cerebral cortex of Alzheimer's patients. The decrease was also found in the nucleus basalis of meynert. The decrease of serotonin in the hypothalamus subregio varies, the maximum reduction in the anterior hypothalamus, while in the posterior hypothalamus peraventrikuler reduced very minimal. This serotonergic cortical changes associated with loss of neurons and filled by NFT formation in the nucleus dorsalis rephe
e. MAO (monoamine oxidase)
       Mitochondrial enzyme MAO will oxidize mono amine transmitter. Normal activity of MAO divided into 2 groups: MAO A for deamination of serotonin, dopamine norepineprin and fraction, whereas MAO B to deamination particularly dopamine.
In patients with Alzheimer's disease, was found in the hypothalamus increased MAO A and MAO B frontais while increased in the temporal region and decreased in the nucleus basalis of meynert.
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