• Archives of neurology · Aug 2012

    Randomized Controlled Trial Multicenter Study

    Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease.

    • Kaj Blennow, Henrik Zetterberg, Juha O Rinne, Stephen Salloway, Jenny Wei, Ronald Black, Michael Grundman, Enchi Liu, and AAB-001 201/202 Investigators.
    • Clinical Neurochemistry Laboratory, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. kaj.blennow@neuro.gu.se
    • Arch. Neurol. 2012 Aug 1; 69 (8): 1002-10.

    BackgroundGiven the slow and variable clinical course of Alzheimer disease, very large and extended clinical trials are needed to identify a beneficial clinical effect of disease-modifying treatments. Therefore, biomarkers are essential to prove that an anti-β-amyloid (Aβ) drug candidate affects both Aβ metabolism and plaque load as well as downstream pathogenic mechanisms.ObjectiveTo evaluate the effect of the anti-Aβ monoclonal antibody bapineuzumab on cerebrospinal fluid (CSF) biomarkers reflecting Aβ homeostasis, neuronal degeneration, and tau-related pathology in patients with Alzheimer disease.DesignTwo phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trials of 12-month duration.SettingAcademic centers in the United States (Study 201) and England and Finland (Study 202).PatientsForty-six patients with mild to moderate Alzheimer disease.InterventionsPatients received either placebo (n = 19) or bapineuzumab (n = 27) in 3 or 4 ascending dose groups.Main Outcome MeasuresChanges between end of study and baseline in the exploratory CSF biomarkers Aβ1-42, AβX-42, AβX-40; total tau (T-tau); and phosphorylated tau (P-tau).ResultsWithin the bapineuzumab group, a decrease at end of study compared with baseline was found both for CSF T-tau (-72.3 pg/mL) and P-tau (-9.9 pg/mL). When comparing the treatment and placebo groups, this difference was statistically significant for P-tau (P = .03), while a similar trend for a decrease was found for T-tau (P = .09). No clear-cut differences were observed for CSF Aβ.ConclusionsTo our knowledge, this study is the first to show that passive Aβ immunotherapy with bapineuzumab results in decreases in CSF T-tau and P-tau, which may indicate downstream effects on the degenerative process. Cerebrospinal fluid biomarkers may be useful to monitor the effects of novel disease-modifying anti-Aβ drugs in clinical trials. TRIAL REGISTRATIONS clinicaltrials.gov Identifier: NCT00112073, EudraCT Identifier: 2004-004120-12, and isrctn.org Identifier: ISRCTN17517446.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…