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Cerebrospinal Fluid Levels of β-Amyloid 1-42, but Not of Tau, Are Fully Changed Already 5 to 10 Years Before the Onset of Alzheimer Dementia.

Buchhave, Peder LU ; Minthon, Lennart LU ; Zetterberg, Henrik; Wallin, Åsa LU ; Blennow, Kaj and Hansson, Oskar LU (2012) In Archives of General Psychiatry 69(1). p.98-106
Abstract
CONTEXT:

Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease.

OBJECTIVES:

To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD.

DESIGN:

A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years).

SETTING:

Memory disorder clinic. Patients A total of 137 patients... (More)
CONTEXT:

Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease.

OBJECTIVES:

To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD.

DESIGN:

A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years).

SETTING:

Memory disorder clinic. Patients A total of 137 patients with MCI who underwent lumbar puncture at baseline. Main Outcome Measure Conversion to AD dementia.

RESULTS:

During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P < .001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development of AD within 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%.

CONCLUSIONS:

Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Archives of General Psychiatry
volume
69
issue
1
pages
98 - 106
publisher
American Medical Association
external identifiers
  • wos:000298675700012
  • pmid:22213792
  • scopus:84855304100
ISSN
0003-990X
DOI
10.1001/archgenpsychiatry.2011.155
language
English
LU publication?
yes
id
fecfa6b6-590f-4fdb-9ce1-c2d2b6ffcb06 (old id 2336752)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22213792?dopt=Abstract
date added to LUP
2012-02-01 19:13:41
date last changed
2017-11-12 03:00:46
@article{fecfa6b6-590f-4fdb-9ce1-c2d2b6ffcb06,
  abstract     = {CONTEXT: <br/><br>
Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease.<br/><br>
OBJECTIVES:<br/><br>
To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development of AD dementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD.<br/><br>
DESIGN:<br/><br>
A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years).<br/><br>
SETTING:<br/><br>
Memory disorder clinic. Patients A total of 137 patients with MCI who underwent lumbar puncture at baseline. Main Outcome Measure Conversion to AD dementia.<br/><br>
RESULTS:<br/><br>
During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P &lt; .001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted to AD within 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development of AD within 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%.<br/><br>
CONCLUSIONS:<br/><br>
Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration.},
  author       = {Buchhave, Peder and Minthon, Lennart and Zetterberg, Henrik and Wallin, Åsa and Blennow, Kaj and Hansson, Oskar},
  issn         = {0003-990X},
  language     = {eng},
  number       = {1},
  pages        = {98--106},
  publisher    = {American Medical Association},
  series       = {Archives of General Psychiatry},
  title        = {Cerebrospinal Fluid Levels of β-Amyloid 1-42, but Not of Tau, Are Fully Changed Already 5 to 10 Years Before the Onset of Alzheimer Dementia.},
  url          = {http://dx.doi.org/10.1001/archgenpsychiatry.2011.155},
  volume       = {69},
  year         = {2012},
}