- Head of Neuropathology research in Oxford Parkinson's Disease Centre
Development of novel, human brain pathology-targeted genetic and biochemical biomarkers for Parkinson’s disease and dementia
After graduating from King’s College London with degrees in Pharmacology (BSc) and Neuroscience (MSc), Laura returned to Finland, where she obtained her PhD in Experimental Neuropathology in 2005 in the University of Kuopio. Her PhD and early postdoctoral work produced indisputable data demonstrating some inadequacies of currently accepted paradigms in the clinico-pathological correlations of Parkinson’s disease (PD) from which she received a Franz Nissl Young Investigator Award given by the International Society of Neuropathology.
From 2005-2008, Laura worked for the Brain Net Europe consortium harmonizing the diagnosis of PD-related pathologies. She returned to UK in 2008 to work as a post-doctoral fellow in the Queen Square Brain Bank, University College London studying various neuropathological substrates of Levodopa treatment, dementia, visual hallucinations and glucocerebrosidase mutations in PD. Laura has worked in four different brain banks (Finland, Barcelona, UCL, Oxford) which has given her a solid understanding on many practical issues varying from donation programs to methodology and diagnostic work.
Since joining the NDCN in 2010, her work has been funded by the £5 million Monument Discovery Award from Parkinson’s UK to Oxford Parkinson’s Disease Centre and this funding was renewed for 2015-2010 (£5.8 million). She was also independently awarded with a Biomarker project grant 2015-2016 ($400.000) from Michael J Fox Foundation and a TreatER project grant 2017-2019 (total 6 million €) from EU Horizon 2020. Laura is a member of Academic committee for the British Neuropathological Society and member of Grant Advisory Board of Parkinson’s UK as well as Assessment Panel of Parkinson’s UK-MS Society Brain Bank.
My research has a unique niche being interdisciplinary between development of genetic and biochemical biomarkers for Parkinson’s disease (PD) and dementia and diagnostic/molecular neuropathology. My overall ambition is to achieve a collective genetic/biochemical signature to assist with early diagnosis of PD and assessing the efficacy of disease-modifying therapies in a biologically-targeted manner.
I am trying to dissect genetic profiles that drive the spread of PD pathology by using digital pathology that allows automated high-throughput quantitative analysis of PD pathology in a large, already genotyped cohorts of donated brains (n>1000). On the other hand, I am also using a technique called laser micro-dissection and subsequent molecular biology techniques (RNA-Seq) in order to understand why certain neurons are more vulnerable than others in PD.
We have recently developed a novel diagnostic tool, measuring the seeding capacity of aSyn protein (RT-QUIC) in cerebrospinal fluid showing high sensitivity and specificity for PD and related synucleinopathies. Our assay also detects subjects with REM sleep behaviour disorder (RBD), at 80% risk of future conversion to a synucleinopathy suggesting that it may have potential as an early diagnostic test for prodromal disease. Therefore, we are currently working to validate this assay as an early, progression and stratifying biomarker as well as assessing its utility in more accessible peripheral tissues.
In addition, we are part of a large, multi-centre EU Horizon 2020 TreatER project studying a new drug for PD; CDNF (Cerebral Dopamine Neurotrophic Factor) which is administered directly into the brains of PD patients using a device specially designed for such procedure by Renishaw in UK. Using human post mortem tissue and in vivo CSF samples, we are studying the potential role of CDNF and related molecules as biomarkers in PD and trying to further elucidate the mechanisms of their target engagement.
Heritability and genetic variance of dementia with Lewy bodies.
Guerreiro R. et al, (2019), Neurobiol Dis, 127, 492 - 501
A comprehensive screening of copy number variability in dementia with Lewy bodies.
Kun-Rodrigues C. et al, (2019), Neurobiol Aging, 75, 223.e1 - 223.e10
Detection of alpha-synuclein conformational variants from gastro-intestinal biopsy tissue as a potential biomarker for Parkinson's disease.
Ruffmann C. et al, (2018), Neuropathol Appl Neurobiol, 44, 722 - 736
LRP10 in α-synucleinopathies
Guerreiro R. et al, (2018), The Lancet Neurology, 17, 1032 - 1033
Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study.
Guerreiro R. et al, (2018), Lancet Neurol, 17, 64 - 74