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Prediction of Alzheimer's disease using a cerebrospinal fluid pattern of C-terminally truncated beta-amyloid peptides

Hoglund, K; Hansson, Oskar LU ; Buchhave, Peder LU ; Zetterberg, H; Lewczuk, P; Londos, Elisabet LU ; Blennow, K; Minthon, Lennart LU and Wiltfang, J (2008) In Neurodegenerative Diseases 5(5). p.268-276
Abstract
Background: Identifying individuals at high risk of developing Alzheimer's disease (AD) is important for future therapeutic strategies, and there is a clinical need for diagnostic biomarkers to identify incipient AD. Objective: The aim of the present study was to investigate if the AD-associated A beta peptide pattern recently found in cerebrospinal fluid (CSF) could discriminate between patients with incipient AD and those with stable mild cognitive impairment (MCI) by analyzing CSF from patients with MCI at baseline. Methods: The levels of A beta(1-37,-38,-39,-40,-42) were analyzed by A beta-SDS-PAGE/immunoblot in CSF from 19 healthy controls, 25 patients with stable MCI and from 25 patients with MCI who later developed AD during 4-to... (More)
Background: Identifying individuals at high risk of developing Alzheimer's disease (AD) is important for future therapeutic strategies, and there is a clinical need for diagnostic biomarkers to identify incipient AD. Objective: The aim of the present study was to investigate if the AD-associated A beta peptide pattern recently found in cerebrospinal fluid (CSF) could discriminate between patients with incipient AD and those with stable mild cognitive impairment (MCI) by analyzing CSF from patients with MCI at baseline. Methods: The levels of A beta(1-37,-38,-39,-40,-42) were analyzed by A beta-SDS-PAGE/immunoblot in CSF from 19 healthy controls, 25 patients with stable MCI and from 25 patients with MCI who later developed AD during 4-to 6-year follow-up. Results:All healthy controls and 20 out of 22 patients who developed AD were correctly classified by their baseline A beta peptide pattern. In 9 out of 25 stable MCI patients, the pattern indicated incipient AD in spite of clinical nonconversion. Interestingly, these individuals had apolipoprotein E genotypes and CSF levels of tau and phospho-tau that are known to be associated with high risk of AD. Conclusion: Altogether, our study reveals the novel finding that the A beta peptide pattern is able to predict AD in patients with MCI with a sensitivity of 91% and specificity of 64%. The specificity would increase to 94% if the high-risk patients in the stable MCI cohort developed AD during extended follow-up. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mild cognitive impairment, pattern, peptide, cerebrospinal fluid, Alzheimer's disease, beta-amyloid, biomarkers
in
Neurodegenerative Diseases
volume
5
issue
5
pages
268 - 276
publisher
Karger
external identifiers
  • wos:000257097900002
  • scopus:44649183443
ISSN
1660-2862
DOI
10.1159/000119457
language
English
LU publication?
yes
id
da5056df-b21d-4df6-8959-abf345aa79bc (old id 1186669)
date added to LUP
2008-09-03 16:05:37
date last changed
2017-09-03 03:48:44
@article{da5056df-b21d-4df6-8959-abf345aa79bc,
  abstract     = {Background: Identifying individuals at high risk of developing Alzheimer's disease (AD) is important for future therapeutic strategies, and there is a clinical need for diagnostic biomarkers to identify incipient AD. Objective: The aim of the present study was to investigate if the AD-associated A beta peptide pattern recently found in cerebrospinal fluid (CSF) could discriminate between patients with incipient AD and those with stable mild cognitive impairment (MCI) by analyzing CSF from patients with MCI at baseline. Methods: The levels of A beta(1-37,-38,-39,-40,-42) were analyzed by A beta-SDS-PAGE/immunoblot in CSF from 19 healthy controls, 25 patients with stable MCI and from 25 patients with MCI who later developed AD during 4-to 6-year follow-up. Results:All healthy controls and 20 out of 22 patients who developed AD were correctly classified by their baseline A beta peptide pattern. In 9 out of 25 stable MCI patients, the pattern indicated incipient AD in spite of clinical nonconversion. Interestingly, these individuals had apolipoprotein E genotypes and CSF levels of tau and phospho-tau that are known to be associated with high risk of AD. Conclusion: Altogether, our study reveals the novel finding that the A beta peptide pattern is able to predict AD in patients with MCI with a sensitivity of 91% and specificity of 64%. The specificity would increase to 94% if the high-risk patients in the stable MCI cohort developed AD during extended follow-up.},
  author       = {Hoglund, K and Hansson, Oskar and Buchhave, Peder and Zetterberg, H and Lewczuk, P and Londos, Elisabet and Blennow, K and Minthon, Lennart and Wiltfang, J},
  issn         = {1660-2862},
  keyword      = {mild cognitive impairment,pattern,peptide,cerebrospinal fluid,Alzheimer's disease,beta-amyloid,biomarkers},
  language     = {eng},
  number       = {5},
  pages        = {268--276},
  publisher    = {Karger},
  series       = {Neurodegenerative Diseases},
  title        = {Prediction of Alzheimer's disease using a cerebrospinal fluid pattern of C-terminally truncated beta-amyloid peptides},
  url          = {http://dx.doi.org/10.1159/000119457},
  volume       = {5},
  year         = {2008},
}