PEN-2 gene mutation in a familial Alzheimer's disease case.

Abstract:

:Genetic evidence indicates a central role of cerebral accumulation of beta-amyloid (Abeta) 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 gamma-secretase activity, the enzymatic complex generating Abeta. 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 epsilon4 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.

journal_name

J Neurol

journal_title

Journal of neurology

authors

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

doi

10.1007/s00415-005-0799-7

keywords:

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

1033-6

issue

9

eissn

0340-5354

issn

1432-1459

journal_volume

252

pub_type

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