The APP and PS1/2 Mutations Linked to Early Onset Familial Alzheimer’s Disease Increase the Extracellular Concentration of Aβ1–42(43)

  • S. G. Younkin
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)


The amyloid β protein (Aβ) is an ~4 kD secreted protein that is derived from a set of large, alternatively spliced precursor proteins collectively referred to as the amyloid β protein precursor (βAPP). Secreted Aβ is readily detected in cerebrospinal fluid (CSF), plasma, and medium conditioned by cultured cells (Seubert et al. 1992; Shoji et al. 1992; Haass et al. 1992; Busciglio et al. 1993). Most secreted Aβ is Aβ1-40, but a small component (5-10%) is Aβ1–42 (Dovey et al. 1993; Vigo-Pelfrey et al. 1993; Suzuki et al. 1994). A large amount of amyloid β protein (Aβ) is deposited extracellularly in the senile plaques that are invariably observed in the brains of patients with all forms of Alzheimer’s disease (AD). Aβ1-42 appears to be particularly important in AD because it forms insoluble amyloid fibrils more rapidly than Aβ1-40 in vitro (Hilbich etal. 1991; Burdick et al. 1992; Jarrett et al. 1993; Jarrett and Lansbury 1993) and is deposited early and selectively in senile plaques (Iwatsubo et al. 1995). Extracellular Aβ deposition could be 1) an essential early event in AD pathogenesis, 2) an “innocent” marker that is invariably associated with some other change that drives AD pathogenesis, or 3) an unimportant, end-stage consequence of AD pathology. To examine the importance of Aβ in AD, we have analyzed the effect of the amyloid β protein (APP; Goate et al. 1991; Mullan et al. 1992), presenilin 1 (PS1; Sherrington et al. 1995) and presenilin 2 (PS2; Levey-Lahad et al. 1995; Rogaev et al. 1995) mutations that are known to cause early onset familial AD (FAD) on extracellular Aβ concentration.


ApoE Genotype Symptomatic Carrier Insoluble Amyloid Fibril Early Onset Familial Alzheimer Disease Early Onset Familial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg New York 1998

Authors and Affiliations

  • S. G. Younkin
    • 1
  1. 1.Mayo Clinic JacksonvilleJacksonvilleUSA

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