Alzheimer’s disease produces chemical markers years before symptoms
18 December 2011
A new study suggests that Alzheimer’s disease is preceded by
the presence of particular chemicals in the blood. These indicators can
be analysed by a simple biochemical analysis of a blood serum sample
months or even years before the first symptoms of the disease occur.
In a healthcare setting, the application of such an assay could
therefore complement the neurocognitive assessment by the medical
doctor and could be applied to identify the at-risk patients in need
of further comprehensive follow-up.
Alzheimer’s disease (AD) is a growing challenge to the healthcare
systems and economies of developed countries. Millions of patients
suffer from this disease and increasing numbers of new cases
diagnosed annually with the increasing ageing of populations.
The progression of Alzheimer’s disease is gradual, with the
subclinical stage of illness believed to span several decades. The
pre-dementia stage, also termed mild cognitive impairment (MCI), is
characterised by subtle symptoms that may affect complex daily
activities. MCI is considered as a transition phase between normal
aging and AD. MCI confers an increased risk of developing AD,
although the state is heterogeneous with several possible outcomes,
including even improvement back to normal cognition.
The team of researchers led by Matej Orešič from the VTT
Technical Research Centre of Finland and Hilkka Soininen from the
University of Eastern Finland set out to study the molecular changes
and processes which define those MCI patients who are at high risk
of developing AD. The results were published on 13th Dec. 2011 in
The team used metabolomics, a high-throughput method for
detecting small metabolites, to produce profiles of the serum
metabolites associated with progression to AD. Serum samples were
collected at baseline when the patients were diagnosed with AD, MCI,
or identified as healthy controls. 52 out of 143 MCI patients
progressed to AD during the follow-up period of 27 months on
A molecular signature comprising three metabolites measured at
baseline was derived which was predictive of progression to AD.
Furthermore, analysis of data in the context of metabolic pathways
revealed that pentose phosphate pathway was associated with
progression to AD, also implicating the role of hypoxia and
oxidative stress as early disease processes.
The unique study setting allowed the researchers to identify the
patients diagnosed with MCI at baseline who later progressed to AD
and to derive the molecular signature which can identify such
patients at baseline.
Though there is no current therapy to prevent AD, early disease
detection is vital both for delaying the onset of the disease
through pharmacological treatment and/or lifestyle changes and for
assessing the efficacy of potential AD therapeutic agents. The
elucidation of early metabolic pathways associated with progression
to Alzheimer’s disease may also help in identifying new therapeutic
This study was supported by the project “From patient data to
personalised healthcare in Alzheimer's disease” (PredictAD) which
was supported by the European Commission under the 7th Framework
M. Orešič, T. Hyötyläinen, S.-K. Herukka, M. Sysi-Aho, I. Mattila,
T. Seppänan-Laakso, V. Julkunen, P. V. Gopalacharyulu, M.
Hallikainen, J. Koikkalainen, M. Kivipelto, S. Helisalmi, J.
Lötjönen, H. Soininen, Metabolome in progression to Alzheimer’s
disease, Translational Psychiatry (2011) 1, e57;