|  NEW INSIGHTS ON PATHOGENESIS OF ALZHEIMER'S DISEASE Alzheimer's disease is a progressive, degenerative and irreversible brain disorder that causes intellectual impairment. When it was first described by the German physician, Alois Alzheimer, in 1907, Alzheimer's disease was considered to be a rare disorder. However, this disease affects an estimated 2.5 million of American adults. Alzheimer's Disease has a gradual onset. An important constituent of the neuritic plaques is, amyloid (Glenner et al, 1984), a set of oligopeptides of about 40 to 43 amino acids, that are proteolytically derived from a much larger-amyloid precursor protein (APP). This precursor which is the product of a single gene, exists in several alternatively spliced forms that code for type I integral proteins of the plasma membrane (Selkoe et al, 1994). Amyloid consists of about 28 amino acids of the large amino-terminal extracellular domain of APP and the first 12 to 15 amino acids of its adjoining membrane-spanning region.The microtubule-associated protein, tau, in abnormally hyperphosphorylated form is the major protein subunit of the neurofibrillary tangles of paired helical filaments. In the August issue of Nature Medicine, Wang et al, showed that these tangles isolated from brains of Alzheimer's disease patients are glycosylated. On the other hand, no glycan was detected in the normal tau.The authors suggested that, although the abnormal phosphorylation might promote aggregation of tau and inhibition of the assembly of microtubules, glycosylation appears to be responsible for the maintenance of the PHF structure. In the familial form of Alzheimer's disease, mutations in three proteins presenilin 1, presenilin 2 and amyloid beta-protein precursor (APP) have been reported. D. Scheune et al reported in the August issue of Nature Medicine that such mutations may all cause Alzheimer's disease by increasing the extracellular concentration of Amyloid-beta42(43) and therefore lead to the deposition of this highly amyloidogenic peptide in the brain. Symptoms of the disease include difficulty with memory and loss of intellectual abilities severe enough to interfere with the routine work or social activities. Patients with Alzheimer's disease (AD) exhibit progressive dementia and the gradual formation of extracellular neuritic plaques in the brain, particularly in the hippocampus and adjoining cortex. The 10 cardinal features of Alzheimer's disease are as follows:
A complete physical, psychiatric and neurologic evaluation by a physician experienced in the diagnosis of dementing disorders should be obtained when symptoms are noticed. At this time, there is no single diagnostic test for Alzheimer's Disease. However, scientists at Harvard have introduced a new test for early diagnosis of Alzheimer's disease. One of the main obstacles in research in Alzheimer's disease is lack of animal models for the disease. In the Oct 4, 96 issue of Science, Hsiao et al reported the creation of a transgenic model of Alzheimer's disease. These transgenic mice overexpress the 695-amino acid isoform of human Alzheimer's amyloid precursor protein which contained a mutation. Initially, these animals exhibited normal learning and memory. However, at the age of nine months, they developed learning and memory deficits which was associated with an increase in the amount of amyloid beta. These animals had numerous amyloid beta positive plaques in cortical and limbic structures which stained with Congo red. These transgenic mice should make it possible to examine the behavioral, biochemical, and pathological abnormalities of Alzheimer's disease under controlled conditions. REFERENCES:
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Poor or decreased judgement
