PMID- 10439444
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20190718
IS  - 0959-4965 (Print)
IS  - 0959-4965 (Linking)
VI  - 10
IP  - 11
DP  - 1999 Aug 2
TI  - A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's
      disease.
PG  - 2255-60
AB  - Mutation in the presenilin-1 (PS-1) gene at chromosome 14q24.3 is the most common
      cause of autosomal dominant early-onset Alzheimer's disease. Here, we report a
      novel missense mutation in the presenilin-1 gene found in a three-generation
      Danish family with autopsy-verified early-onset Alzheimer's disease. Two affected
      first-degree relatives in two generations were found to be heterozygous for a
      cytosine to adenine transversion at the second position of codon 116, which
      changes the amino acid at that position from threonine to asparagine. This
      conservative amino acid substitution occurs in an evolutionary highly conserved
      region of the PS-1 protein and is associated with onset of the disease between
      age 35 and 41 years and 4-8 years' duration of the disease. Analysis of amyloid
      beta-protein (A beta) deposition in brain specimens from one affected family
      member showed predominance of A beta 42(43). Onset and progression of the disease
      were very similar in two sibs homozygous for the epsilon 3 allele and the epsilon
      4 allele, respectively, of the polymorphic apolipoprotein E locus. The lack of
      effect of the high risk epsilon 4/epsilon 4 genotype on the disease in this
      family corroborates and extends previous observations that the presence of one
      copy of the epsilon 4 allele does not modulate PS-1 associated Alzheimer's
      disease.
FAU - Romero, I
AU  - Romero I
AD  - Department of Human Genetics, University of Aarhus, Denmark.
FAU - Jorgensen, P
AU  - Jorgensen P
FAU - Bolwig, G
AU  - Bolwig G
FAU - Fraser, P E
AU  - Fraser PE
FAU - Rogaeva, E
AU  - Rogaeva E
FAU - Mann, D
AU  - Mann D
FAU - Havsager, A M
AU  - Havsager AM
FAU - Jorgensen, A L
AU  - Jorgensen AL
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neuroreport
JT  - Neuroreport
JID - 9100935
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Membrane Proteins)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Presenilin-1)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Alzheimer Disease/*epidemiology/*etiology
MH  - *Amino Acid Substitution
MH  - Amyloid beta-Peptides/metabolism
MH  - Apolipoproteins E/genetics
MH  - Brain/metabolism
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Mutation/genetics
MH  - Pedigree
MH  - Peptide Fragments/metabolism
MH  - Presenilin-1
EDAT- 1999/08/10 00:00
MHDA- 1999/08/10 00:01
CRDT- 1999/08/10 00:00
PHST- 1999/08/10 00:00 [pubmed]
PHST- 1999/08/10 00:01 [medline]
PHST- 1999/08/10 00:00 [entrez]
AID - 10.1097/00001756-199908020-00006 [doi]
PST - ppublish
SO  - Neuroreport. 1999 Aug 2;10(11):2255-60. doi: 10.1097/00001756-199908020-00006.