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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.
Arch Gen Psychiatry 2012; 69(1):98-106AG

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 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.

Authors+Show Affiliations

Neuropsychiatric Clinic, Skåne University Hospital, Malmö, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22213792

Citation

Buchhave, Peder, et al. "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." Archives of General Psychiatry, vol. 69, no. 1, 2012, pp. 98-106.
Buchhave P, Minthon L, Zetterberg H, et al. 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. Arch Gen Psychiatry. 2012;69(1):98-106.
Buchhave, P., Minthon, L., Zetterberg, H., Wallin, A. K., Blennow, K., & Hansson, O. (2012). 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. Archives of General Psychiatry, 69(1), pp. 98-106. doi:10.1001/archgenpsychiatry.2011.155.
Buchhave P, et al. 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. Arch Gen Psychiatry. 2012;69(1):98-106. PubMed PMID: 22213792.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Buchhave,Peder, AU - Minthon,Lennart, AU - Zetterberg,Henrik, AU - Wallin,Asa K, AU - Blennow,Kaj, AU - Hansson,Oskar, PY - 2012/1/4/entrez PY - 2012/1/4/pubmed PY - 2012/2/23/medline SP - 98 EP - 106 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 69 IS - 1 N2 - 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. SN - 1538-3636 UR - https://www.unboundmedicine.com/medline/citation/22213792/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_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=22213792.ui DB - PRIME DP - Unbound Medicine ER -