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Longitudinal changes of CSF biomarkers in Alzheimer's disease.

Abstract

Longitudinal changes of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) have been studied, but there are few consistent conclusions and even less is known about their variation during the different stages of the disease. We hypothesized that changes in CSF biomarker values would correlate with the progression of the cognitive decline in AD. One hundred and thirty-one memory clinic patients [56 AD, 57 mild cognitive impairment (MCI), 10 other neurological disorders, eight unimpaired subjects] underwent a clinical follow-up with repeated Mini-Mental Status Examination (MMSE) tests and two lumbar punctures with a median interval of 3 years. Levels of CSF amyloid-β (Aβ)(42), tau, and p-tau-181 were measured using commercially available ELISA. Twenty-one of the MCI subjects progressed to AD, whereas 26 subjects remained stable and 56 subjects had AD already at the baseline. The subjects displaying the most rapid MMSE decline rate had the lowest baseline Aβ(42), highest tau, and highest p-tau-181 CSF concentrations. An annual decrease of 2.20 pg/ml/year in the CSF p-tau-181 concentration was seen in AD-AD patients (p = 0.001). The difference was significant compared to stable MCI-MCI (increase of 1.24 pg/ml/year, p = 0.001) and cognitively healthy (increase of 0.84 pg/ml/year, p = 0.013) subjects (p for group difference 0.004). The decrease rate of p-tau-181 correlated with the MMSE decrease rate in AD subjects (r = 0.579, p < 0.001). The CSF Aβ(42) level decreased in the AD-AD group (decrease 11.9 pg/ml/year, p < 0.001). Concentrations of hyperphosphorylated tau decline in the late stages of the AD process. The decrease of p-tau-181 appears to correlate with cognitive functioning and probably reflects neuronal loss. More longitudinal studies of CSF biomarker dynamics are needed, especially in patients during the preclinical stage of the disease.

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  • Authors+Show Affiliations

    ,

    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland. toni.seppala@fimnet.fi

    , , , ,

    Source

    MeSH

    Aged
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoproteins E
    Biomarkers
    Cognition
    Cognitive Dysfunction
    Cross-Sectional Studies
    Disease Progression
    Enzyme-Linked Immunosorbent Assay
    Female
    Humans
    Longitudinal Studies
    Male
    Neuropsychological Tests
    Peptide Fragments
    tau Proteins

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    21460434

    Citation

    Seppälä, Toni T., et al. "Longitudinal Changes of CSF Biomarkers in Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 25, no. 4, 2011, pp. 583-94.
    Seppälä TT, Koivisto AM, Hartikainen P, et al. Longitudinal changes of CSF biomarkers in Alzheimer's disease. J Alzheimers Dis. 2011;25(4):583-94.
    Seppälä, T. T., Koivisto, A. M., Hartikainen, P., Helisalmi, S., Soininen, H., & Herukka, S. K. (2011). Longitudinal changes of CSF biomarkers in Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 25(4), pp. 583-94. doi:10.3233/JAD-2011-101911.
    Seppälä TT, et al. Longitudinal Changes of CSF Biomarkers in Alzheimer's Disease. J Alzheimers Dis. 2011;25(4):583-94. PubMed PMID: 21460434.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Longitudinal changes of CSF biomarkers in Alzheimer's disease. AU - Seppälä,Toni T, AU - Koivisto,Anne M, AU - Hartikainen,Päivi, AU - Helisalmi,Seppo, AU - Soininen,Hilkka, AU - Herukka,Sanna-Kaisa, PY - 2011/4/5/entrez PY - 2011/4/5/pubmed PY - 2011/12/13/medline SP - 583 EP - 94 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 25 IS - 4 N2 - Longitudinal changes of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) have been studied, but there are few consistent conclusions and even less is known about their variation during the different stages of the disease. We hypothesized that changes in CSF biomarker values would correlate with the progression of the cognitive decline in AD. One hundred and thirty-one memory clinic patients [56 AD, 57 mild cognitive impairment (MCI), 10 other neurological disorders, eight unimpaired subjects] underwent a clinical follow-up with repeated Mini-Mental Status Examination (MMSE) tests and two lumbar punctures with a median interval of 3 years. Levels of CSF amyloid-β (Aβ)(42), tau, and p-tau-181 were measured using commercially available ELISA. Twenty-one of the MCI subjects progressed to AD, whereas 26 subjects remained stable and 56 subjects had AD already at the baseline. The subjects displaying the most rapid MMSE decline rate had the lowest baseline Aβ(42), highest tau, and highest p-tau-181 CSF concentrations. An annual decrease of 2.20 pg/ml/year in the CSF p-tau-181 concentration was seen in AD-AD patients (p = 0.001). The difference was significant compared to stable MCI-MCI (increase of 1.24 pg/ml/year, p = 0.001) and cognitively healthy (increase of 0.84 pg/ml/year, p = 0.013) subjects (p for group difference 0.004). The decrease rate of p-tau-181 correlated with the MMSE decrease rate in AD subjects (r = 0.579, p < 0.001). The CSF Aβ(42) level decreased in the AD-AD group (decrease 11.9 pg/ml/year, p < 0.001). Concentrations of hyperphosphorylated tau decline in the late stages of the AD process. The decrease of p-tau-181 appears to correlate with cognitive functioning and probably reflects neuronal loss. More longitudinal studies of CSF biomarker dynamics are needed, especially in patients during the preclinical stage of the disease. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/21460434/Longitudinal_changes_of_CSF_biomarkers_in_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-2011-101911 DB - PRIME DP - Unbound Medicine ER -