Open AccessCSF beta‐amyloid 1–42 – what are we measuring in Alzheimer's disease?
Author(s) -
Hu William T.,
Watts Kelly D.,
Shaw Leslie M.,
Howell Jennifer C.,
Trojanowski John Q.,
Basra Sundeep,
Glass Jonathan D.,
Lah James J.,
Levey Allan I.
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.160
Subject(s) - cerebrospinal fluid , medicine , apolipoprotein e , biomarker , dementia , endocrinology , alzheimer's disease , disease , biology , biochemistry
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 ) ε 4 allele, AD diagnosis, A β ‐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 (A β 42), 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 A β 42 levels measured using the AD Neuro‐imaging Initiative ( ADNI ) protocol (which we call suspended A β 42 or susA β ) were lower than total measurable CSF A β 42 in all groups, and on average represents 57% of the latter. Logistic regression analysis showed this proportion (% susA β ) to be directly correlated with CSF A β 42 and apoJ levels, but inversely correlated with CSF t‐Tau levels. Finally, we showed in vitro that increasing apoE and apoJ levels directly increased % susA β . Conclusion CSF susA β levels are influenced by biological and technical factors, and may represent a marker of A β susceptible to lipoprotein‐mediated clearance. Clinical trials should include total measurable A β 42 and susA β to better inform outcomes.