CSF beta-amyloid 1–42 – what are we measuring in Alzheimer's disease?

William T. Hu, Kelly D. Watts, Leslie M. Shaw, Jennifer C. Howell, John Q. Trojanowski, Sundeep Basra, Jonathan D. Glass, James J. Lah, Allan I. Levey

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Objective: To characterize biological and technical factors which influence cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker levels, including the presence of apolipoprotein E (APOE) ε4 allele, AD diagnosis, Aβ-binding proteins, sample processing, and preanalytical handling. Methods: CSF was collected from 140 subjects with normal cognition, mild cognitive impairment, AD, and non-AD dementia. CSF levels of beta-amyloid 1–42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) were analyzed following the standard and modified protocols. CSF levels of apoJ, apoE, albumin, and α-synuclein were measured in a subgroup (n = 69), and their effects on measured AD biomarker levels were also determined in vitro using human CSF samples. Results: CSF Aβ42 levels measured using the AD Neuro-imaging Initiative (ADNI) protocol (which we call suspended Aβ42 or susAβ) were lower than total measurable CSF Aβ42 in all groups, and on average represents 57% of the latter. Logistic regression analysis showed this proportion (% susAβ) to be directly correlated with CSF Aβ42 and apoJ levels, but inversely correlated with CSF t-Tau levels. Finally, we showed in vitro that increasing apoE and apoJ levels directly increased % susAβ. Conclusion: CSF susAβ levels are influenced by biological and technical factors, and may represent a marker of Aβ susceptible to lipoprotein-mediated clearance. Clinical trials should include total measurable Aβ42 and susAβ to better inform outcomes.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalAnnals of Clinical and Translational Neurology
Volume2
Issue number2
DOIs
StatePublished - Feb 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology

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