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Fish model of Alzheimer's Pathology
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Alzheimer’s Disease (AD), which is clinically characterized by a gradual deterioration of cognitive function, is the most common form of dementia (Brookmeyer et al. 1998). It affects approximately 7-10% of individuals over the age of 65, and as many as 40% of individuals over the age of 80. These demographics are expected to grow, as average life expectancy continues to increase, and a growing percentage of the population is above the age of 65 years (Sisodia 1999). Pathologically, AD is characterized by three forms of neurodegeneration: intraneuronal neurofibrillary tangles, dystrophic neurons, and extracellular amyloid deposits in cerebral vessels and neuritic plaques (Selkoe et al. 1986). Cerebral amyloid deposits consist primarily of b-amyloid peptide (Ab), which can aggregate spontaneously to form fibrils that deposit in the extra-cellular tissue spaces and cerebral vasculature. This peptide ranges in size from 39-43 amino acids (the most common form being Ab1-42) and is generated from the proteolysis of amyloid precursor protein (APP; Glenner and Wong 1984). APP is a large integral membrane protein that exists in numerous different isoforms (Gandy 1994); APP695 is most selectively expressed in neurons and is the isoform primarily found in the human brain (Wisniewski et al. 1997). It has been reported that Ab in the brain is constitutively formed during normal cellular metabolism (Haass et al.1992) and may play an important physiological role throughout life. Potential functions have been suggested, including growth factor (Beeson et al.
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