Supplementary Table 2 | Criteria for an ideal biomarker for AD
Criteria for an ideal diagnostic
Current status for CSF biomarkers
marker
Detect a fundamental feature of the
Autopsy and PIB-PET studies have shown that
molecular pathogenesis or
CSF A 1–42 is a marker of fibrillar amyloid
neuropathology of AD
pathology in the brain1–4
Several lines of evidence show that CSF t-tau
reflects the intensity of axonal degeneration
and damage,5–11 although the release of tau
from tangle-bearing neurons might contribute2
Autopsy studies show that CSF p-tau reflects
tangle pathology in the brain2,12
Validated in neuropathologically
Several studies based on patient series with
confirmed AD cases
autopsy-confirmed diagnoses have verified the
high sensitivity and specificity of CSF
biomarkers in differentiating patients with AD
from cognitively normal elderly individuals and
patients with other forms of dementia13–17
Have a sensitivity >80% for detecting Numerous studies have shown that CSF
AD and a specificity >80% for
biomarkers have sensitivity and specificity
differentiating AD from other
values in the context of AD in the range of 80–
dementias
90%;18,19 such value have been shown in large
prospective studies20
Be able to detect AD in its early
Several large multicenter studies have shown
stages (i.e. during MCI)
that CSF biomarkers have a high predictive
value for identifying prodromal AD in cases of
MCI14,21,22
Be reliable
Data on analytical methods is available for
both ELISA and xMAP methods (Luminex,
Austin, TX, USA), with both approaches
showing excellent antibody specificity and
assay performance23–25
Within-assay and within-laboratory variation
for the biomarker assays are low, but
between-laboratory variation is high, which
highlights a need for standardization26
Be noninvasive
LP can be regarded as a moderately invasive
procedure,27 but large prospective studies
show that there are no serious complications
of this approach, and that the risk of post-LP
headache in patients admitted for evaluation of
cognitive symptoms is very low28–30
Be simple to perform, inexpensive
ELISAs are part of the standard analytical
and, thus, adaptable in routine
techniques used in clinical laboratories; CSF
clinical practice
biomarkers are increasingly used in clinical
practice31,32
These criteria were outlined by the Ronald and Nancy Reagan Research Institute–
National Institute on Aging Working Group on Biomarkers for AD.27 Abbreviations: AD,
Alzheimer disease; CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent
assay; LP, lumbar puncture; MCI, mild cognitive impairment; PIB, Pittsburgh
compound B; p-tau, phosphorylated tau; t-tau, total tau.
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