New potential avenues for early disease detection
A study led by Research Professor Matej Oresic from VTT suggests that
Alzheimer´s disease is preceded by a molecular signature indicative of hypoxia
and up-regulated pentose phosphate pathway. This indicator can be analysed as
a simple biochemical assay from a 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 health care systems and
economies of developed countries with millions of patients suffering from this
disease and increasing numbers of new cases diagnosed annually with the
increasing ageing of populations.
The progression of
Alzheimer’s disease (AD) 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.
What are the
molecular changes and processes which define those MCI patients who are at
high risk of developing AD? The teams led by Matej Orešič from VTT and Hilkka
Soininen from the University of Eastern Finland set out to address this
question, and the results were published on 13th Dec. 2011 in Translational
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 average. 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
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
Reference: 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; doi:10.1038/tp.2011.55.