The PSEN1 I143T mutation in a Swedish family with Alzheimer's disease: clinical report and quantification of A beta in different brain regions
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1720939
- author
- Keller, Lina ; Welander, Hedvig ; Chiang, Huei-Hsin ; Tjernberg, Lars O. ; Nennesmo, Inger ; Wallin, Åsa LU and Graff, Caroline
- organization
- publishing date
- 2010
- 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
- pmid:20628413
- 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
- 2016-04-01 10:56:28
- date last changed
- 2022-01-26 03:51:42
@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}},
keywords = {{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}},
doi = {{10.1038/ejhg.2010.107}},
volume = {{18}},
year = {{2010}},
}