Zerr_ EU Neuro Rev_EU Neurology 11/03/2010 12:38 Page 19
Transthyretin Cerebrospinal Fluid Levels in Alzheimer’s Disease
reduced in comparison with patients without dementia.
13,22,27
Other another study that analysed tau, Aβ
1–42
and TTR in the same
studies have reported decreased TTR concentrations in the CSF of population, clear differences between biomarkers were elucidated.
patients with depression and normal pressure hydrocephalus Whereas no association of dementia severity with tau and Aβ
1–42
(NPH).
28,30
Although hampered by an artificial study design, similar levels were detected, this was clearly observed for TTR: patients with
results were achieved for post mortem CSF in AD.
31
In other severe AD showed a significantly lower TTR concentration (p=0.05)
neurodegenerative diseases, normal concentrations of TTR are compared with mild cognitive impairment or mild dementia. At a cut-
detected.
30
Table 1 summarises the data available on TTR from off of 15mg/l both stages could be discriminated, with a sensitivity of
CSF studies. TTR levels are significantly reduced in the CSF of patients 91% and a specificity of 75% (Youden=0.66). Such an effect was not
with AD and NPH compared with controls and other dementia, and seen in patients with NPH (see Figure 2).
30
In summary, TTR levels have
TTR CSF values in AD did not differ significantly from those in NPH been demonstrated to be selectively decreased in AD compared with
patients (see Figure 1).
30
TTR levels did not correlate with tau, other dementias. In addition, some data indicate that levels reflect
Aβ
1–40
or Aβ
1–42
CSF.
30
disease severity in AD, which makes this protein an interesting
biomarker for AD diagnosis. Studies on early AD stages are lacking so
Several attempts have been made to identify parameters that might far, and more must follow. n
reflect disease severity in AD. Studies on this subject are limited and
contradictory results have been obtained so far. Both positive
and negative associations have been reported. Increased levels of
Inga Zerr is a Professor in the Department of Neurology at the University Medical
School, Georg-August University Göttingen. She is Head of the Dementia Outpatients
p-tau and tau were reported to reflect disease severity in AD in a study
Section and Head of the National Reference Centre for Prion Diseases in Germany. Her
that analysed the abundance of symptoms in AD and low levels of major research interests include early biomarker development in dementia, at
Aβ
proteomic, genomic or brain imaging levels. Professor Zerr holds various national and
1–42
. The investigators found a higher risk of early death in AD in
international grants on prion diseases and dementia research and is co-ordinating an
those with low Aβ
1–42
, and the follow-up patients who died had
EC-funded project on biomarker development. She studied medicine at the Georg
significantly lower levels of Aβ
1–42
and significantly higher August University in Göttingen, where she started her scientific career in the
concentrations of tau.
32
By contrast, Haense et al.
33
found no
Department of Neurology in 1993.
associations between tau and p-tau with dementia severity in AD. In
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