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Original Research Article
Dement Geriatr Cogn Disord 2006;22:48–53
DOI: 10.1159/000093261
Stability of CSF -Amyloid
1–42
and Tau
Levels by APOE Genotype in Alzheimer
Patients
Edward D. Huey
a
Nadeem Mirza
a
Karen T. Putnam
a
Holly Soares
c
Gyorgy Csako
b
James A. Levy
a
Brittany Copenhaver
a
Robert M. Cohen
a
Trey Sunderland
a
a
Geriatric Psychiatry Branch,
b
Department of Laboratory Medicine, W.G. Magnuson Clinical Center,
National Institute of Mental Health, Bethesda, Md., and
c
Pharmacogenomics and Clinical Biochemical
Measurements Division, Pfizer Central Research, Groton, Conn., USA
Introduction
Alzheimer’s disease (AD) is associated with neurof-
brillary tangles composed of microtubule-associated pro-
tein tau and the formation of plaques consisting primar-
ily of -amyloid peptides. As new medications for AD are
developed (e.g., secretase inhibitors, amyloid immuniza-
tion), the correct early diagnosis of AD will become cru-
cial, and CSF biomarkers will likely be a useful aid for
early diagnosis. Prior to their clinical use, however, bio-
markers should be shown to be informative over the
course of the illness. High concentrations of tau and ab-
normally low concentrations of -amyloid
1–42
in the ce-
rebrospinal fuid (CSF) show promise as diagnostic tests
for AD [1, 2], but their stability over time in AD and the
efect of the APOE 4 allele, known to increase suscepti-
bility to AD, on these measurements are not clear [3–8].
Tis experiment tests the stability over time, and the efect
of APOE genotype, on CSF tau and -amyloid
1–42
.
Te period of time previous authors have assessed the
stability of CSF biomarkers has generally been 1–2 years
[3–7], with one study measuring CSF -amyloid and tau
for a mean period of 3 years [8] . Similarly, our laboratory
found stability of CSF tau protein in mild-to-moderate
AD patients over 2 years despite signifcant clinical pro-
Key Words
Alzheimer disease diagnostic tests Cerebrospinal fluid
biomarker -Amyloid Tau APOE genotype
Abstract
Background: Cerebrospinal fluid (CSF) measures of -amy-
loid
1–42
and tau differ between patients with Alzheimer’s Dis-
ease (AD) and elderly normal controls. The effect of time and
APOE genotype on these biomarkers continues to be eluci-
dated. Methods: We assessed CSF -amyloid
1–42
and tau in
20 mild-to-moderate AD patients, 11 APOE 4+ and 9 APOE
4–, over a mean time of 3.8 years (range 1–11.1 years). Re-
sults: Over the period measured, CSF -amyloid
1–42
levels
were lower in APOE 4+ compared to APOE 4– patients, and
the levels decreased over time. Tau levels were stable over
time and did not show an effect of APOE allele. Conclusions:
While this is a limited clinical sample, the further decrease in
CSF -amyloid
1–42
(i.e., more abnormal) combined with the
CSF tau stability over a mean period of almost 4 years sug-
gests that -amyloid
1–42
and tau maintain their potential
usefulness as diagnostic biomarkers over time. These find-
ings should be taken into account if CSF -amyloid
1–42
and
tau are used as measures of treatment response.
Copyright © 2006 S. Karger AG, Basel
Accepted: December 18, 2005
Published online: May 8, 2006
Edward D. Huey, MD
Fellow, Cognitive Neuroscience Section
National Institute of Neurological Disorders and Stroke
Bldg. 10, Room 5C205, MSC 1440, Bethesda, MD 20892 (USA)
Tel. +1 301 402 2584, Fax +1 301 480 2909, E-Mail hueye@ninds.nih.gov
© 2006 S. Karger AG, Basel
1420–8008/06/0221–0048$23.50/0
Accessible online at:
www.karger.com/dem