uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Low prevalence of APP duplications in Swedish and Finnish patients with early onset Alzheimer's disease
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Show others and affiliations
2008 (English)In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 16, no 2, 171-5 p.Article in journal (Refereed) Published
Abstract [en]

Familial early-onset Alzheimer's disease with cerebral amyloid angiopathy (EOAD/CAA) was recently associated with duplications of the gene for the amyloid-beta precursor protein (APP). In this study, we have screened for duplications of APP in patients with EOAD from Sweden and Finland. Seventy-five individuals from families with EOAD and 66 individuals with EOAD without known familial inheritance were screened by quantitative PCR. On the basis of the initial results, a portion of the samples was also investigated with quantitative multiplex PCR. No duplications of APP were identified, whereby we conclude that this is not a common cause of EOAD in the Swedish and Finnish populations, at least not in our collection of families and cases.

Place, publisher, year, edition, pages
2008. Vol. 16, no 2, 171-5 p.
Keyword [en]
early-onset Alzheimer's disease, amyloid beta precursor protein, gene dose, APP, duplication
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97805DOI: 10.1038/sj.ejhg.5201966ISI: 000252426500007PubMedID: 18043715OAI: oai:DiVA.org:uu-97805DiVA: diva2:172882
Available from: 2008-11-21 Created: 2008-11-21 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Genetic Studies of Alzheimer's Disease
Open this publication in new window or tab >>Genetic Studies of Alzheimer's Disease
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with Alzheimer's disease (AD) often have a family history of the disease, implicating genetics as a major risk factor. Three genes are currently known to cause familial early-onset AD (<65 years): the amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2). For the much more common late-onset disease (>65 years), only the APOE gene has repeatedly been associated to AD, where the ε4 allele increases disease risk and decreases age at onset. As APOE ε4 only explains part of the total estimated disease risk, more genes are expected to contribute to AD.

This thesis has focused on the study of genetic risk factors involved in AD. In the first study, we conducted a linkage analysis of six chromosomes previously implicated in AD in a collection of affected relative pairs from Sweden, the UK and the USA. An earlier described linkage peak on chromosome 10q21 could not be replicated in the current sample, while significant linkage was demonstrated to chromosome 19q13 where the APOE gene is located. The linkage to 19q13 was further analyzed in the second study, demonstrating no significant evidence of genes other than APOE contributing to this peak.

In the third study, the prevalence of APP duplications, a recently reported cause of early-onset AD, was investigated. No APP duplications were identified in 141 Swedish and Finnish early-onset AD patients, implying that this is not a common disease mechanism in the Scandinavian population.

In the fourth study, genes with altered mRNA levels in the brain of a transgenic AD mouse model (tgAPP-ArcSwe) were identified using microarray analysis. Differentially expressed genes were further analyzed in AD brain. Two genes from the Wnt signaling pathway, TCF7L2 and MYC, had significantly increased mRNA levels in both transgenic mice and in AD brains, implicating cell differentiation and possibly neurogenesis in AD.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 401
Keyword
Alzheimer's disease, Linkage, Affected sib-pairs, APOE, APP duplication, 10q21, 19q13, Wnt signaling
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-9397 (URN)978-91-554-7346-4 (ISBN)
Public defence
2008-12-12, the Rudbeck hall, Rudbeck laboratory, Dag Hammarskjölds väg 20, Uppsala, 13:15
Opponent
Supervisors
Available from: 2008-11-21 Created: 2008-11-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Geriatrics
In the same journal
European Journal of Human Genetics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 489 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf