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The PSEN1 I143T mutation in a Swedish family with Alzheimer's disease: clinical report and quantification of A beta in different brain regions

Keller, Lina; Welander, Hedvig; Chiang, Huei-Hsin; Tjernberg, Lars O.; Nennesmo, Inger; Wallin, Åsa LU and Graff, Caroline (2010) In European Journal of Human Genetics 18(11). p.1202-1208
Abstract
Early-onset dominantly inherited forms of Alzheimer's disease (AD) are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and PSEN2, alter the APP processing and lead to an increased amyloid beta-peptide (A beta) 42/40 ratio. This, together with other studies on pathogenic mechanisms, show that A beta 42 is a major player in the etiology of AD. Here, we present a clinical and neuropathological description of a Swedish family with an I143T mutation in the PSEN1 gene, which gives rise to a severe form of AD. We also performed an extensive investigation on the concentration and distribution of A beta species of... (More)
Early-onset dominantly inherited forms of Alzheimer's disease (AD) are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and PSEN2, alter the APP processing and lead to an increased amyloid beta-peptide (A beta) 42/40 ratio. This, together with other studies on pathogenic mechanisms, show that A beta 42 is a major player in the etiology of AD. Here, we present a clinical and neuropathological description of a Swedish family with an I143T mutation in the PSEN1 gene, which gives rise to a severe form of AD. We also performed an extensive investigation on the concentration and distribution of A beta species of different lengths in six brain regions from two mutation carriers. Our study showed that A beta 42 and a longer peptide, A beta 43, were present both in plaque cores and in total amyloid preparations, and were each clearly more frequent than A beta 40 in all examined regions, as shown by both mass spectrometry and immunohistochemistry. European Journal of Human Genetics (2010) 18, 1202-1208; doi: 10.1038/ejhg.2010.107; published online 14 July 2010 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mass spectrometry, amyloid beta-peptide variants, Alzheimer's disease, PSEN1 mutations, neuropathology
in
European Journal of Human Genetics
volume
18
issue
11
pages
1202 - 1208
publisher
Nature Publishing Group
external identifiers
  • wos:000283314700007
  • scopus:77958507752
ISSN
1476-5438
DOI
10.1038/ejhg.2010.107
language
English
LU publication?
yes
id
2a301076-2684-4863-9d62-fb08c31ce8ca (old id 1720939)
date added to LUP
2010-12-03 14:08:02
date last changed
2018-06-24 03:30:30
@article{2a301076-2684-4863-9d62-fb08c31ce8ca,
  abstract     = {Early-onset dominantly inherited forms of Alzheimer's disease (AD) are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and PSEN2, alter the APP processing and lead to an increased amyloid beta-peptide (A beta) 42/40 ratio. This, together with other studies on pathogenic mechanisms, show that A beta 42 is a major player in the etiology of AD. Here, we present a clinical and neuropathological description of a Swedish family with an I143T mutation in the PSEN1 gene, which gives rise to a severe form of AD. We also performed an extensive investigation on the concentration and distribution of A beta species of different lengths in six brain regions from two mutation carriers. Our study showed that A beta 42 and a longer peptide, A beta 43, were present both in plaque cores and in total amyloid preparations, and were each clearly more frequent than A beta 40 in all examined regions, as shown by both mass spectrometry and immunohistochemistry. European Journal of Human Genetics (2010) 18, 1202-1208; doi: 10.1038/ejhg.2010.107; published online 14 July 2010},
  author       = {Keller, Lina and Welander, Hedvig and Chiang, Huei-Hsin and Tjernberg, Lars O. and Nennesmo, Inger and Wallin, Åsa and Graff, Caroline},
  issn         = {1476-5438},
  keyword      = {mass spectrometry,amyloid beta-peptide variants,Alzheimer's disease,PSEN1 mutations,neuropathology},
  language     = {eng},
  number       = {11},
  pages        = {1202--1208},
  publisher    = {Nature Publishing Group},
  series       = {European Journal of Human Genetics},
  title        = {The PSEN1 I143T mutation in a Swedish family with Alzheimer's disease: clinical report and quantification of A beta in different brain regions},
  url          = {http://dx.doi.org/10.1038/ejhg.2010.107},
  volume       = {18},
  year         = {2010},
}