Journal of Neurology

, Volume 252, Issue 9, pp 1033–1036

PEN–2 gene mutation in a familial Alzheimer’s disease case

  • C. Sala Frigerio*
  • P. Piscopo*
  • E. Calabrese
  • A. Crestini
  • L. Malvezzi Campeggi
  • R. Civita di Fava
  • S. Fogliarino
  • D. Albani
  • G. Marcon
  • R. Cherchi
  • R. Piras
  • G. Forloni
  • A. Confaloni
ORIGINAL COMMUNICATION

DOI: 10.1007/s00415-005-0799-7

Cite this article as:
Sala Frigerio*, C., Piscopo*, P., Calabrese, E. et al. J Neurol (2005) 252: 1033. doi:10.1007/s00415-005-0799-7
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Abstract

Genetic evidence indicates a central role of cerebral accumulation of β–amyloid (Aβ) in the pathogenesis of Alzheimer’s disease (AD). Beside presenilin 1 and 2, three other recently discovered proteins (Aph 1, PEN 2 and nicastrin) are associated with γ–secretase activity, the enzymatic complex generating Aβ. Alterations in genes encoding these proteins were candidates for a role in AD. The PEN 2 gene was examined for unknown mutations and polymorphisms in sporadic and familial Alzheimer patients. Samples from age–matched controls (n = 253), sporadic AD (SAD, n = 256) and familial AD (FAD, n = 140) were screened with DHPLC methodology followed by sequencing. Scanning the gene identified for the first time a missense mutation (D90N) in a patient with FAD. Three intronic polymorphisms were also identified, one of which had a higher presence of the mutated allele in AD subjects carrying the allele ε4 of apolipoprotein E than controls. The pathogenic role of the PEN–2 D90N mutation in AD is not clear, but the findings might lead to new studies on its functional and genetic role.

Key words

β–amyloid genetics γ–secretase mutation 

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • C. Sala Frigerio*
    • 1
  • P. Piscopo*
    • 2
  • E. Calabrese
    • 3
  • A. Crestini
    • 2
  • L. Malvezzi Campeggi
    • 2
  • R. Civita di Fava
    • 2
  • S. Fogliarino
    • 1
  • D. Albani
    • 1
  • G. Marcon
    • 4
  • R. Cherchi
    • 5
  • R. Piras
    • 5
  • G. Forloni
    • 1
  • A. Confaloni
    • 2
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri”MilanoItaly
  2. 2.Dept. of Cellular Biology and NeuroscienzeIstituto Superiore di SanitàRomeItaly
  3. 3.IRCCS S. Maria NascenteMilanItaly
  4. 4.DPMSCUniversità di UdineUdineItaly
  5. 5.Clinica Neurologica University of SassariSassariItaly

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