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Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study.

Abstract

BACKGROUND

Disease-modifying treatment strategies for Alzheimer's disease have led to an urgent need for biomarkers to identify the disease at a very early stage. Here, we assess the association between CSF biomarkers and incipient Alzheimer's in patients with mild cognitive impairment (MCI).

METHODS

From a series of 180 consecutive patients with MCI, we assessed 137 who underwent successful lumbar puncture at baseline. Patients at risk of developing dementia were followed clinically for 4-6 years. Additionally, 39 healthy individuals, cognitively stable over 3 years, served as controls. We analysed CSF concentrations of beta amyloid(1-42) (Abeta42), total tau (T-tau), and phosphorylated tau (P-tau181) using Luminex xMAP technology.

FINDINGS

During follow-up, 57 (42%) patients with MCI developed Alzheimer's disease, 21 (15%) developed other forms of dementia, and 56 (41%) remained cognitively stable for 5.2 years (range 4.0-6.8). A combination of CSF T-tau and Abeta42 at baseline yielded a sensitivity of 95% and a specificity of 83% for detection of incipient AD in patients with MCI. The relative risk of progression to Alzheimer's disease was substantially increased in patients with MCI who had pathological concentrations of T-tau and Abeta42 at baseline (hazard ratio 17.7, p<0.0001). The association between pathological CSF and progression to Alzheimer's disease was much stronger than, and independent of, established risk factors including age, sex, education, APOE genotype, and plasma homocysteine. The combination of T-tau and Abeta42/P-tau181 ratio yielded closely similar results (sensitivity 95%, specificity 87%, hazard ratio 19.8).

INTERPRETATION

Concentrations of T-tau, P-tau181, and Abeta42 in CSF are strongly associated with future development of Alzheimer's disease in patients with MCI.

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  • Authors+Show Affiliations

    ,

    Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.

    , , , ,

    Source

    The Lancet. Neurology 5:3 2006 Mar pg 228-34

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid beta-Peptides
    Analysis of Variance
    Biomarkers
    Chi-Square Distribution
    Cognition Disorders
    Dementia
    Female
    Follow-Up Studies
    Humans
    Male
    Middle Aged
    Neurofibrillary Tangles
    Odds Ratio
    Peptide Fragments
    Phosphorylation
    Psychiatric Status Rating Scales
    Retrospective Studies
    Time Factors
    tau Proteins

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    16488378

    Citation

    Hansson, Oskar, et al. "Association Between CSF Biomarkers and Incipient Alzheimer's Disease in Patients With Mild Cognitive Impairment: a Follow-up Study." The Lancet. Neurology, vol. 5, no. 3, 2006, pp. 228-34.
    Hansson O, Zetterberg H, Buchhave P, et al. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5(3):228-34.
    Hansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., & Minthon, L. (2006). Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. The Lancet. Neurology, 5(3), pp. 228-34.
    Hansson O, et al. Association Between CSF Biomarkers and Incipient Alzheimer's Disease in Patients With Mild Cognitive Impairment: a Follow-up Study. Lancet Neurol. 2006;5(3):228-34. PubMed PMID: 16488378.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. AU - Hansson,Oskar, AU - Zetterberg,Henrik, AU - Buchhave,Peder, AU - Londos,Elisabet, AU - Blennow,Kaj, AU - Minthon,Lennart, PY - 2006/2/21/pubmed PY - 2006/4/13/medline PY - 2006/2/21/entrez SP - 228 EP - 34 JF - The Lancet. Neurology JO - Lancet Neurol VL - 5 IS - 3 N2 - BACKGROUND: Disease-modifying treatment strategies for Alzheimer's disease have led to an urgent need for biomarkers to identify the disease at a very early stage. Here, we assess the association between CSF biomarkers and incipient Alzheimer's in patients with mild cognitive impairment (MCI). METHODS: From a series of 180 consecutive patients with MCI, we assessed 137 who underwent successful lumbar puncture at baseline. Patients at risk of developing dementia were followed clinically for 4-6 years. Additionally, 39 healthy individuals, cognitively stable over 3 years, served as controls. We analysed CSF concentrations of beta amyloid(1-42) (Abeta42), total tau (T-tau), and phosphorylated tau (P-tau181) using Luminex xMAP technology. FINDINGS: During follow-up, 57 (42%) patients with MCI developed Alzheimer's disease, 21 (15%) developed other forms of dementia, and 56 (41%) remained cognitively stable for 5.2 years (range 4.0-6.8). A combination of CSF T-tau and Abeta42 at baseline yielded a sensitivity of 95% and a specificity of 83% for detection of incipient AD in patients with MCI. The relative risk of progression to Alzheimer's disease was substantially increased in patients with MCI who had pathological concentrations of T-tau and Abeta42 at baseline (hazard ratio 17.7, p<0.0001). The association between pathological CSF and progression to Alzheimer's disease was much stronger than, and independent of, established risk factors including age, sex, education, APOE genotype, and plasma homocysteine. The combination of T-tau and Abeta42/P-tau181 ratio yielded closely similar results (sensitivity 95%, specificity 87%, hazard ratio 19.8). INTERPRETATION: Concentrations of T-tau, P-tau181, and Abeta42 in CSF are strongly associated with future development of Alzheimer's disease in patients with MCI. SN - 1474-4422 UR - https://www.unboundmedicine.com/medline/citation/16488378/Association_between_CSF_biomarkers_and_incipient_Alzheimer's_disease_in_patients_with_mild_cognitive_impairment:_a_follow_up_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(06)70355-6 DB - PRIME DP - Unbound Medicine ER -