Study reveals genetic clues underlying progressive supranuclear palsy
20 June 2011
Scientists are one step closer to understanding the genes associated with the rare neurodegenerative disease, progressive supranuclear palsy (PSP), according to a study published in the current Nature Genetics. The genomewide association study was completed by an international consortium of researchers, including members of UCL Institute of Neurology’s Reta Lila Weston Institute (RLWI).
Progressive supranuclear palsy (PSP) is a parkinsonian
movement disorder, affecting around 3-6 people per 100,000, and
characterised by difficulty coordinating eye movement, imbalance and
gait instability, still movements and emotional changes.
In the past two decades, scientists have been able to ascertain that patients with PSP show an abnormal accumulation of the tau protein in their brain (a protein also associated with Alzheimer’s disease) and that the risk of developing PSP is increased in patients with common variation in the gene that codes for tau, MAPT. So while data suggests that an increase in tau protein production is a factor in developing PSP, it is not clear whether this causes PSP.
With advances in microarray-based technology that allow
scientists to get a snapshot of the 20,000-25,000 genes and non-coding
regions between the genes, this study compared the genetic variations
between about 2,100 individuals with PSP to normal control subjects. The
technology allows scientists to identify genetics variants that are
over- or under-represented in the disease group and thereby pinpoint the
affected genes. However, due to the very small effect size of these
associations and because PSP is a relatively rare disorder, a large
number of disease and control subjects was needed to obtain
statistically meaningful results. A vast team of researchers from
European and American clinical and scientific centres worked together to
complete the study, including a large contribution of autopsy confirmed
samples from the RLWI and Queen Square Brain Bank.
The results of the study reiterate the role of the MAPT
gene in PSP and confirm that patients with the MAPT H1 haplotype variant
have increased risk of PSP. It also identified several other gene
regions associated with the risk of developing PSP: the MOPB gene
(involved in myelin formation), the STX6 gene (which may change
intracellular transport or cause toxic absorption) and the EIF2AK3 gene
(which is involved in the clean up of potentially toxic misfolded
These findings provide researchers with new avenues for the
study of the causes of PSP, and potentially lead to the investigation
of new drug discovery targets.
The consortium was headed by Professor Jerry Schellenberg,
University of Pennsylvania and included members of RLWI (Dr Rohan de
Silva, Professors John Hardy and Andrew Lees). The project was funded by
the CurePSP Foundation and the Peebler PSP Research Foundation.
Research at the RLWI and Queen Square Brain Bank are funded by The PSP
Association and Brain Research Trust.