ORIGINAL ARTICLE
Correlations between serum levels of beta amyloid,
cerebrospinal levels of tau and phospho tau, and delayed
response tasks in young and aged cynomolgus monkeys
(Macaca fascicularis)
H.S. Darusman
1,2
, D. Sajuthi
3
, O. Kalliokoski
1
, K.R. Jacobsen
1
, J. Call
4
, S.J. Schapiro
1,5
,
A. Gjedde
6,7,8
, K.S.P. Abelson
1
& J. Hau
1
1 Department of Experimental Medicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
2 Department of Anatomy, Physiology and Pharmacology, Faculty of Veterinary Medicine, Bogor Agricultural University, Bogor, Indonesia
3 Primate Research Center, Bogor Agricultural University, Bogor, Indonesia
4 Max Planck Institute of Evolutionary Anthropology, Leipzig, Germany
5 Department of Veterinary Sciences, The University of Texas MD Andersson Cancer Center, Bastrop, TX, USA
6 Department of Neuroscience and Pharmacology, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
7 Center for Functionally Integrative Neuroscience, University of Aarhus, Aarhus, Denmark
8 Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA
Keywords
aging – Alzheimer’s disease – biomarker –
memory test
Correspondence
Prof. Jann Hau, MD, Department of
Experimental Medicine, Faculty of Health
Science, University of Copenhagen, Panum
Institute building 16.1, Blegdamsvej 3B, DK
2200 Copenhagen, Denmark.
Tel.: +45 35 32 73 73;
fax: +45 35 32 73 99;
e-mail: jhau@sund.ku.dk
Accepted February 26, 2013.
Abstract
Background In an attempt to explore cynomolgus monkeys as an animal
model for Alzheimer’s disease, the present study focused on the Alzheimer’s
biomarkers beta amyloid 1–42 (Ab
42
) in serum, and total tau (t-tau) and
phosphorylated tau (p-tau) levels in cerebrospinal fluid.
Methods We measured biomarker levels in Young and Aged cynomolgus
monkeys and correlated these with performance on three delayed response
tasks.
Results The Ab
42
concentration of the Aged monkeys was significantly lower
than in the Young subjects, while the t-tau and p-tau did not significantly dif-
fer between the groups. The Young subjects performed significantly better
than the Aged individuals on the memory tests. Only Ab
42
levels were signifi-
cantly correlated with performance in the three delayed response tasks.
Conclusions Circulating Ab
42
levels were lower in Aged monkeys and were
correlated with inferior performance on delayed response tasks in Aged ani-
mals; therefore, both measures may be useful in establishing cynomolgus
monkeys as models for studies of AD.
Introduction
With an aging population and the associated increased
social and economic burden on society, great efforts are
needed to better diagnose and effectively treat Alzhei-
mer’s disease (AD) [1]. AD is regarded as the most com-
mon cause of progressive cognitive impairments and
dementia in aged human patients [2, 3]. While the cur-
rent treatment strategies for AD emphasize early diag-
nosis and treatment, the pathological process of the
disease is noticeable only when it manifests clinically,
shortly before significant cognitive decline occurs. Since
their discovery in 1907 [4], amyloid plaques and neurofi-
brillary tangles (NFT) have been the hallmark histo-
pathological features of AD. Neurons of the medial
temporal lobe and hippocampus are subject to deterio-
ration that seems to coincide with the onset of clinically
significant cognitive impairment [5]. The National Insti-
tute of Neurological and Communicative Disorders and
Stroke and Alzheimer’s Disease and Related Disorders
Association (NINCDS-ADRDA) has set several criteria
for diagnosing AD based on measurements of cognitive
J Med Primatol 42 (2013) 137–146
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 137
J Med Primatol doi:10.1111/jmp.12044