Alzheimer¡¦s disease (AD) was first reported and named after the patient in 1907, Alois Alzheimer. It is the leading cause of dementia in the world, affecting 12 million people worldwide. Symptoms of the disease include memory loss, temporal and geographic disorientation, resulting failure to maintain balance of self, impairment of judgment, deterioration of problem solving, and deterioration of language abilities. AD is caused by the formation of plaque and neurofibrillary tangles (NFTs) leading to extensive neuron death in the brain and results in a destructive pathway. Some other factor causing AD are over expression of amyloid precursor protein (APP), presenilins, or tau protein genes to cause the over-production and build up of the plague. This paper explores these neuro-pathological problems that leads to the developing of AD in rodent transgenic animal and non-rodent transgenic animal such as the fruit fly Drosophila melanogaster and the nematode Ceanorhabditis elegant to learn from and develop treatment and therapy for the human condition (Spires and Hyman, 2005). What¡¦s wrong in the Alzheimer brain
In 1927 Divry showed that the senile plaques in the Alzheimer¡¦s brain is a spherical mass of amyloid fibrils, which is an extracellular aggregation of amyloid that is later on discovered to be derived from the APP by Kang et al. in 1987. In the Alzheimer¡¦s brain, plague formation usually starts first from the basal neocortex of the brain and then spread to the hippocampal formation and adjoining cortical areas of the brain.
Formation of NFTs is another known cause of AD. The neurofibrillary tangles first form in the transentorhinal region and spread through to the entorhinal cortex, hippocampus, association cortex and sensory cortex. This eventually leads to the degradation of temporal lobe memory system and contribute to the memory loss symptom. The density of the NFT is directly related to the disease duration and the severity of dementia. Formation of NFT also mirrors the progression of extensive neuron loss; correspondingly, a case of large-scale loss of neuron will show more dramatic display of the AD symptoms. The remaining neuron in the brain undergoes changes that alter the connectivity in the circuit of dendrite and cell body, resulting in the loss of synapses relates to the cognitive decline. Amyloid Pathology Mouse Models
The over expression of APP in amyloid pathology can cause AD. In 1995, PDAPP mouse was introduced to use as a study tool for AD, these mice over expressed human APP cDNA that had a higher level of APP protein expression by ten fold in comparison to normal mouse. The PDAPP mice expressed very similar property that of the AD in ultra structures, pathway of plaque formation, and even the degeneration of memory by testing with maze task with increase aging.
Other lines of mouse with similar over express of human APP has been developed with slight different mutation or different promoter control for the amyloid precursor protein. These other transgenic mouse shows difference in percentage of neuron loss and plaque formation at different age, however they all show the general memory deficits symptoms expressed like the AD. Interaction of presenilin and APP
APP mutations only cause a fraction of the reason for familial AD. It is believed that mutation in presenilins1 and 2 can also contribute to the cause of AD by altering the process of APP to favor the production of the fibrillogenic A£]42. Crossing of mutant presenilin 1 with Tg C3-3 APP line of mice increase the A£]42 level in the brain and cause accelerated formation of plaque. The AD that¡¦s associated with the mutation of presenilins have a higher probability of producing the A£]42 amino acid that is harmful, making presenilins a drug target to allow further experiment to develop treatment that can decrease amyloid deposition in AD patients. Tau transgenic mouse models
The tau protein binds microtubules,...
Cited: Iijima et al. 2004. Dissecting the pathological effects of human A£]40 and A£]42 in
Drosophila : A potential model for Alzheimer¡¦s disease. Proc. Natl. Acad. Sci. USA. 101(17): 6623-6628.
Spires and Hyman, 2005. Transgenic Models of Alzheimer¡¦s Disease: Learning from Animals. NeuroRx. 2005 July: 423-437.
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