Alzheimer's disease and the amyloid beta protein: What is the role of amyloid?

摘要: Alzheimer’s disease (AD) is characterized by the deposition of amyloid in extracellular compartment brain form congophilic angiopathy (CAA) and plaques (APs). Intracellular neurofibrillary tangles (NFTs) (Terry, 1963) formed from abnormally phosphorylated cytoskeletal protein tau are also seen (Lee et al., 1991). The identification b (Ab) CAA APs (Glenner Wong, 1984; Masters 1985) led to cloning precursor (APP) (Kang 1987). discovery familial AD (FAD) mutations APP gene (Chartier-Harlin 1991; Goate Murrell Naruse Tanzi Hyman, 1991) has supported view that a defect metabolism or function directly involved pathogenesis. demonstration can lead non-Alzheimer dementias with pathology, lacking Ab (reviewed Spillantini Goedert, 1998), reinforced NFTs secondary phenomenon pathogenesis AD. It long been argued an early step (Masters 1985; Hardy Higgins, 1992; Beyreuther, 1993). term refers insoluble proteinaceous deposits exhibit red– green birefringence presence plane polarized light (Kisilevsky, 1994). Implicit much research on role assumption toxic (Jarrett Lansbury, 1993) these underlying cause observation peptides when “aged” (incubated fibrils) become neurons culture (Yankner 1989; Frautschy Kowall Pike Howlett 1995) further this view. cascade hypothesis AD, as formalized Higgins (1992), states “precipitates and, turn, causes cell death.” However, challenged (see, e.g., Davis Chisholm, 1997; Hardy, 1997b). does not correlate dementia (Terry Arriagada Roses, 1994; Samuel Braak Braak, 1996), although failure observe correlation may be related method which AP load measured (Cummings Cotman, 1995). Whether have pathogenic remains controversial issue.