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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2336752
- author
- Buchhave, Peder
LU
; Minthon, Lennart
LU
; Zetterberg, Henrik
; Wallin, Åsa
LU
; Blennow, Kaj
and Hansson, Oskar
LU
- organization
- publishing date
- 2012
- 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
- 2016-04-01 09:50:52
- date last changed
- 2022-05-17 17:32:34
@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 < .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}},
doi = {{10.1001/archgenpsychiatry.2011.155}},
volume = {{69}},
year = {{2012}},
}