The Alzheimer disease-associated amyloid beta protein precursor gene and familial Alzheimer disease.
The application of recombinant DNA techniques to AD and DS pathogenesis have provided the molecular biological reagents necessary to delineate the crucial events in the neurodegenerative process in these disorders. Critical issues which remain to be solved include: which form of APP gives rise to beta amyloid deposits and from what cells is it derived? How is APP normally processed and degraded, and does its metabolism differ in various brain regions and cell types in AD and DS patients? Is amyloid toxic to neurons and able to induce NFT formation characteristic of dying neurons or is amyloid simply a secondary by-product of degenerating neurons and nerve terminals in affected regions of AD and DS brain? What is the physical relationship between intracellular amyloid and NFT and how are NFT involved with neuronal cell death? Answers to these questions should elucidate the final events in the degenerative process and provide valuable insights into the basic etiology underlying AD and DS. Meanwhile, isolation and identification of the FAD gene defect on chromosome 21 would provide direct information about the primary cause of FAD. Intensive molecular investigations aimed at deciphering the neuropathogenetic process in AD and DS will hopefully provide valuable biological clues about the primary defect in AD as well as ways to ameliorate the symptoms of both AD and DS.
Tanzi
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Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Boston.
D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor; D006801:Humans; D011498:Protein Precursors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors