Genetics of the Alzheimer Amyloid Protein Precursor

  • Rachael L. Neve
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 265)


Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by gradual loss of memory, reasoning, orientation, and judgment (Katzman, 1983). AD generally occurs as a sporadic disorder of unknown cause. However, a proportion of cases, which have been termed familial Alzheimer’s disease (FAD), are caused by a genetic defect that is transmitted in an autosomal dominant fashion (Heston et al., 1981), and that has been mapped to chromosome 21 (St. George-Hyslop, 1987a). One of the hallmarks of AD is the presence of numerous neuritic plaques in postmortem brain tissue that are revealed by neuropathological examination (Glenner, 1983). The degree of intellectual impairment in patients appears to be correlated with the frequency of neuritic plaques in the cortex (Roch et al., 1966). The mature neuritic plaque consists of degenerating axons and neurites surrounding an amyloid plaque core (APC) composed of 5- to 10-nm filaments (Mertz et al., 1983) that stain with Congo red (Terry et al., 1981). Similar filaments are also found outside of plaques as independent bundles in the cortical neuropil and in the walls of meningeal and intracortical blood vessels [termed cerebrovascular amyloid (CVA)] (Glenner, 1983). A 4.2-kD polypeptide, called the β protein (due to its partial β-pleated sheet structure), has been isolated from both CA and APC. An identical 28-amino acid sequence (with the exception of a Glu to Gln substitution) was obtained from the CA and APC β proteins, suggesting a possible common origin for both types of amyloid (Glenner and Wong, 1984a, 1984b; Masters et al., 1985). The brains of aged individuals with Down syndrome (DS, trisomy 21) also have both APC and CA that contain a β protein with the same stretch of 28 amino acids (Glenner and Wong, 1984b; Masters et al., 1985); this similarity indicates that a common mechanism may underlie the formation of amyloid in AD and DS.


Down Syndrome Amyloid Protein Precursor Neuritic Plaque Cornu Ammonis Amyloid Protein Precursor Gene 
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Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Rachael L. Neve
    • 1
  1. 1.Division of GeneticsThe Children’s HospitalBostonUSA

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