Guerreiro Laboratory
OVERVIEW
Genomic Sciences and Neurodegeneration
By 2030, the incidence of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases are expected to rise significantly, underscoring the urgent need to develop improved ways to prevent, slow or stop disease progression.
To this end, the Guerreiro Lab investigates the genetic contributors to both common and rare/familial forms of these diseases. Together with the Brás Lab, they use cutting-edge genetic technologies, such as genome-wide genotyping arrays and next-generation sequencing, to identify genes and specific mutations that give rise to and propel these disorders.
Recently, they and their colleagues have identified several genetic risk factors for Alzheimer’s and Parkinson’s diseases. They also have pinpointed disease-causing genes in several familial forms of neurodegenerative disease, with one of the most significant being the identification of mutations in TREM2 as the cause of a frontotemporal dementia-like phenotype in a group of Turkish families. This finding opened the door to the identification of TREM2 variants as very significant genetic risk factors for Alzheimer’s.
Job Openings
The Guerreiro Lab is looking for motivated individuals with strong publication records to join our lab as postdoctoral fellows. Experience in computational biology, bioinformatics or statistical genetics is required to apply. Additional experience in human molecular genetics and genomics is desirable (but not necessary). Interested candidates should email Dr. Guerreiro to inquire.
Recent News and Featured Publications
Learn More
Seven facts about the human brain
In Portugal, a search for the genetic roots of Alzheimer’s disease
How Big Data and collaboration are redefining a rare form of dementia
Orme T … Guerreiro R, Brás J. 2020. Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies. Acta Neuropathol Commun 8(5).
Sundal C, Carmona S, Yhr M, Almström O, Ljungberg M, Hardy J, Hedberg-Oldfors C, Fred Å, Brás J, Oldfors A, Andersen O, Guerreiro R. 2019. An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids. Acta Neuropathol Commun 7:188.
Moore KM…Guerreiro R, Brás J, Rohrer JD. 2019. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: An international retrospective cohort study. Lancet Neurol.
Our Impact
We’re raising thousands to save millions.
We’re turning hope into action for the millions of people around the world affected by diseases like cancer and Parkinson’s. Find out how you can help us make a difference.
- 118 papers published in 2022
- 48 papers in high-impact journals in 2022
- 42 clinical trials launched
Rita Guerreiro, Ph.D.
Associate Professor, Department of Neurodegenerative Science
Areas of Expertise
Genetics, neurodegeneration, Parkinson’s disease, Alzheimer’s disease, next-generation sequencing, rare neurological diseases
Biography
Dr. Rita Guerreiro is a leader in parsing the genetic variations that contribute to neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. She earned her B.Sc. in biomedical sciences from Coimbra Health Technology Institute, her M.S. degree in biomolecular methods from Aveiro University and her Ph.D. (with honors) from Coimbra University, all in Portugal. Her pre-doctoral work was supervised by Dr. John Hardy and Dr. Catarina Oliveira, and was conducted at the Laboratory of Neurogenetics at the National Institute on Aging, National Institutes of Health. While there, she studied the genetics of dementia, with a focus on searching for new mutations and new genes underlying Alzheimer’s disease and frontotemporal dementia. In 2010, she joined the Department of Molecular Neuroscience at University College London’s Institute of Neurology as a postdoctoral research fellow, where she explored genetic variability in several neurological diseases (mainly Parkinson’s and Alzheimer’s diseases) and investigated how genetic variants affect the disease process at the molecular level. In 2015, she became a principal investigator in the Department of Molecular Neuroscience, after holding a Travelling Research Fellowship US from Alzheimer’s Research UK (2012–2015) and obtaining a Senior Research Fellowship from Alzheimer’s Society (2015–2019). In 2017 she was named programme leader at the UK Dementia Research Institute at University College London. In 2018, she joined Van Andel Institute’s Department of Neurodegenerative Science as an associate professor.
Dr. Guerreiro was the first recipient of the Alzheimer’s Research UK Young Investigator of the Year Award in 2016, and also earned the 2015 Fondazione Gino Galletti Neuroscience Prize and the 2015 Alzheimer’s Society Dementia Research Leaders Award. She was recognized as a Personality of the Year in 2015 by Dr. Anibal Cavaco Silva, president of the Portuguese Republic. In 2014, Dr. Guerreiro received the IFRAD (Fondation pour la Recherche sur Alzheimer) European Grand Prix for Young Researchers.
She serves on the editorial boards of the American Journal of Neurodegenerative Disease, Science Matters, Journal of Alzheimer’s Disease and Journal of Parkinson’s Disease, and is an advisory editor for Neurobiology of Aging.
Selected Publications
Holstege H, Hulsman M, Charbonnier C, Grenier-Boley B, Quenez O, Grozeva D, van Rooij JGJ, Sims R, Ahmad S, Amin N, Norsworthy PJ, Dols-Icardo O, Hummerich H, Kawalia A, Amouyel P, Beechmam GW, Berr C, Bis JC, Boland A, Bossu P, Bouwman F, Brás J, Guerreiro R, Nicolas G, Bellenguez C, Lambert JC. 2022. Exome sequencing identifies rare damaging variants in ATP8b4 and ABCA1 as risk factors for Alzheimer’s disease. Nature Genet 54(12):1786–1794.
Killinger BA, Marshall LL, Chatterjee D, Chu Y, Brás J, Guerreiro R, Kordower JH. 2022. In situ proximity labeling identifies Lewy pathology molecular interactions in the human brain. Proc Natl Acad Sci USA 119(5):e2114405119.
Monkare S, Kuuluvainen L, Schleutker J, Brás J, Roine S, Poyhonen M, Guerreiro R, Myllykangas L. 2022. Genetic analysis reveals novel variants for vascular cognitive impairment. Acta Neurol Scand146(1):42–50.
Pereira-Tabuas M, Santana I, Almeida MR, Durães J, Lima M, Duro D, Kun-Rodrigues C, Brás J, Guerreiro R. 2022. Rare variants in TP73 in a frontotemporal dementia cohort link this gene with primary progressive aphasia phenotypes. Eur J Neurol 29(5):1524–1528.
Reid KM, Spaull R, Salian S, Barwick K, Meyer E, Zhen J, Hirata H, Sheipouri D, Guerreiro R, Brás J, Maher ER, Scott RH, Kurian MA. 2022. MED27, SLC6A7, and MPPE1 variants in a complex neurodevelopmental disorder with severe dystonia. Mov Disord 37(10):2139-–2146.
Tábuas-Pereira M, Guerreiro R, Kun-Rodrigues C, Almeida MR, Brás J, Santana I. 2022. Whole-exome sequencing reveals PSEN1 and ATP7B combined variants as a possible cause of early-onset Lewy body dementia: A case study of genotype-phenotype correlation. Neurogenetics 23(4):279–283.
Tabuas-Pereira M, Santana I, Gibbons E, Paquette K, Almeida MR, Baldeiras I, Brás J, Guerreiro R. 2022. Exome sequencing of a Portuguese cohort of frontotemporal dementia patients: Looking into the ALS-FTD continuum. Front Neurol 13:886379.
Yang CH*, Fagnocchi L*, Apostle S, Wegert V, Casani-Galdón S, Landgraf K, Panzeri I, Dror E, Heyne S, Wörpel T, Chandler DP, Lu D, Yang T, Gibbons E, Guerreiro R, Brás J, Thomasen M, Grunnert LG, Vaag AA, Gillberg L, Grundberg, E, Conesa A, Körner A, PERMUTE, Pospisilik JA. 2022. Independent phenotypic plasticity axes define distinct obesity subtypes. Nat Metab.
*Co-first authorship
**Highlighted in News & Views
. 2022. Molecular characterization of Portuguese patients with hereditary cerebellar ataxia. Cells 11(6):981.
Genome-wide association of polygenic risk extremes for Alzheimer’s disease in the UK Biobank. Sci Rep 12(1):8404.
Hatton C, Ghanem SS, Koss DJ, Abdi IY, Gibbons E, Guerreiro R, Brás J, International DLB Consortium, Walker L, Gelpi E, Heywood W, Outeiro TF, Attems J, McFarland R, Forsyth R, El-Agnaf M, Erskine D. 2022. Prion-like α-synuclein pathology in the brain of infants with Krabbe disease. Brain.
Khani M, Gibbons E, Brás J, Guerreiro R. 2022. Challenge accepted: Uncovering the role of rare genetic variants in Alzhemier’s disease. Mol Neurodegen 17(3).
Dehghani N, Guven G, Kun-Rodrigues C, Gouveia C, Foster K, Hanagasi H, Lohmann E, Samanci B, Gurvit H, Bilgic B, Brás J, Guerreiro R. 2021. A comprehensive analysis of copy number variation in a Turkish dementia cohort. Hum Genom 15:48.
Messerschmidt C, . . ., Brás J, Guerreiro R, Beule D, Dirnagl U, Sassi C. 2021. PHACTR1 genetic variaiblity is not critical in small vessel ischemic disease patients and PcomA recruitment in C57BL/6J mice. Sci Rep.
Dehghani N, Brás J, Guerreiro R. 2021. How understudied populations have contributed to our understanding of Alzheimer’s disease genetics. Brain.
. 2020. KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia. Eur J Neurol 27(8):1471–1477.
Orme T … Guerreiro R, Brás J. 2020. Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies. Acta Neuropathol Commun 8(5).
Sundal C, Carmona S, Yhr M, Almström O, Ljungberg M, Hardy J, Hedberg-Oldfors C, Fred Å, Brás J, Oldfors A, Andersen O, Guerreiro R. 2019. An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids. Acta Neuropathol Commun.
Sundal C, Carmona S, Yhr M, Almström O, Ljungberg M, Hardy J, Hedberg-Oldfors C, Fred Å, Brás J, Oldfors A, Andersen O, Guerreiro R. 2019. An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids. Acta Neuropathol Commun 7:188.
Moore KM…Guerreiro R, Brás J, Rohrer JD. 2019. Age at symptom onset and death and disease duration in genetic frontotemporal dementia: An international retrospective cohort study. Lancet Neurol.
Nalls MA…Singleton AB, System Genomics of Parkinson’s Disease Consortium and International Parkinson’s Disease Genomics Consortium 2019. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neuro.
*Dr. Guerreiro is part of the International Parkinson’s Disease Genomics Consortium
Guven G, Bilgic B, Tufekcioglu Z, Erginel Unaltuna N, Hanagasi H, Gurvit H, Singleton A, Hardy J, Emre M, Gulec C, Brás JM, Guerreiro RJ, Lohmann E. 2018. Peripheral GRN mRNA and serum progranulin levels as a potential indicator for both the presence of splice site mutations and individuals at risk for frontotemporal dementia. J Alz Dis 1–9.
Kia DA, Sabir MS, Ahmed S, Trinh J, Bandres-Ciga S, International Parkinson’s Disease Consortium. 2018. LRP10 in a-synucleinopathies. Lancet Neurol 17(12):1032.
Carmona S, Hardy J, Guerreiro RJ. 2018. The genetic landscape of Alzheimer’s disease. Handb Clin Neurol 148:395–408.
Carmona S, Marecos C, Amorim M, Ferreira AC, Conceição C, Brás JM, Duarte ST, Guerreiro RJ. 2018. AP4S1 splice-site mutation in a case of spastic paraplegia type 52 with polymicrogyria. Neurol Genet 4(5):e273.
Guerreiro RJ, Orme T, Naj AC, Kuzma AB, Schellenberg GD, Brás JM. 2018. Is APOE ε4 required for Alzheimer’s disease to develop in TREM2 p.R47H variant carriers? Neuropathol Appl Neurobiol.
Carmona S, Zahs K, Wu E, Dankin K, Brás JM, Guerreiro RJ. 2018. The role of TREM2 in Alzheimer’s disease and other neurodegenerative disorders. Lancet Neurol 17(8):721–730.
Blauwendraat C, Reed X, Kia DA, Gan-Or Z, Lesage S, Pihlstrøm L, Guerreiro RJ, Gibbs JR, Sabir M, Ahmed S, Ding J, Alcalay RN, Hassin-Baer S, Pittman AM, Brooks J, Edsall C, Hernandez DG, Chung SJ, Goldwurm S, Toft M, Schulte C, Brás JM, Wood NW, Brice A, Morris HR, Scholz SW, Nalls MA, Singleton AB, Cookson MR. 2018. Frequency loss of function variants in LRRK2 in Parkinson disease. JAMA Neurol 75(11):1416–1422.
Kun-Rodrigues C … Guerreiro RJ, Brás JM. 2018. A comprehensive screening of copy number variation in dementia with Lewy bodies. Neurobiol Aging.
Orme T, Guerreiro RJ, Brás J. 2018. The genetics of dementia with Lewy bodies: Current understanding and future directions. Curr Neurol Neurosci Rep. 18(10):67.
Patel T, Brookes KJ, Turton J, Chaudhury S, Guetta-Baranes T, Guerreiro RJ, Brás JM, Hernandez, Singleton A, Francis PT, Hardy J, Morgan K. 2018. Whole-exome sequencing of the BDR cohort: Evidence to support the role of the PILRA gene in Alzheimer’s disease. Neuropathol Appl Neurobiol 44(5):506–521.
Hartl D, May P, Gu W, Mayhaus M, Pichler S, Spaniol C, Glaab E, Bobbili DR, Antony P, Koegelsberger S, Kurz A, Grimmer T, Morgan K, Vardarajan BN, Reitz C, Hardy J, Brás JM, Guerreiro RJ, Balling R, Schneider JG, Riemenschneider M. 2018. A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease. Mol Psych.
Khan RR … Guerreiro RJ, Brás JM … Michael D Greicius. 2018. Stop-gain variant in microglia-expressed gene GMIP is associated with early onset Alzheimer’s disease. Alzheimers Dementia 14(7):1534–1536.
Chaudhury SR, Patel T, Fallows A, Brookes KJ, Guetta-Baranes T, Turton J, Sussams R, Guerreiro RJ, Brás JM, Hardy J, Francis PT, Holmes C, Morgan K. 2018. Alzheimer’s disease polygenic risk score as a predictor of conversion from mild cognitive impairment. Alzheimers Dementia 14(7):1094.
Brainstorm Consortium…Brás JM..Guerreiro RJ…Murray R. 2018. Analysis of shared heritability in common disorders of the brain. Science 360(6395).
Brookes KJ, McConnell G, Williams K, Chaudhury S, Madhan G, Patel T, Turley C, Guetta-Baranes T, Brás JM, Guerreiro RJ, Hardy J, Francis PT, Morgan K. 2018. Genotyping of the Alzheimer’s disease genome-wide association study index single nucleotide polymorphisms in the brains for Dementia Research Cohort. J Alzheimers Dis 64(2):355–362.
Sassi C, Nalls MA, Ridge PG, Gibbs JR, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C, Lord J, Turton J, Brás JM, ARUK Consortium, Blumenau S, Thielke M, Josties C, Freyer D, Dietrich A, Hammer M, Baier M, Dirnagl U, Morgan K, Powell JF, Kauwe JS, Cruchaga C, Goate AM, Singleton AB, Guerreiro RJ, Hodges A, Hardy J. 2018. Mendelian adult-onset leukodystrophy genes in Alzheimer’s disease: critical influence of CSF1R and NOTCH3. Neurobiol Aging 66:179.e1 –179.e29.
Pasanen P, Myllykangas L, Pöyhönen M, Kiviharju A, Siitonen M, Hardy J, Brás JM, Paetau A, Tienari PJ, Guerreiro RJ, Verkkoniemi-Ahola A. 2018. Genetics of dementia in a Finnish cohort. EurJ Hum Genet 26(6).827–837.
Camargos S, Guerreiro RJ, Brás JM, Mageste LS. 2018. Late-onset and acute presentation of Brown-Vialetto-Van Laere syndrome in a Brazilian family. Neurol Genet 4(1):e215.
Rusbridge C, Salguero FJ, David MA, Faller KME, Bras JT, Guerreiro RJ, Richard-Londt AC, Grainger D, Head E, Brandner SGP, Summers B, Hardy J, Tayebi M. 2018. An aged canid with behavioral deficits exhibits blood and cerebrospinal fluid amyloid beta oligomers. Front Aging Neurosci 10:7.
Guerreiro RJ … Brás JM. 2018. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol 17(1):64–74.
Ridge PG, Karch CM, Hsu S, Arano I, Teerlink CC, Ebbert MTW, Gonzalez Murcia JD, Farnham JM, Damato AR, Allen M, Wang X, Harari O, Fernandez VM, Guerreiro RJ, Brás JM, Hardy J, Munger R, Norton M, Sassi C, Singleton A, Younkin SG, Dickson DW, Golde TE, Price ND, Ertekin-Taner N, Cruchaga C, Goate AM, Corcoran C, Tschanz J, Cannon-Albright LA, Kauwe JSK; Alzheimer’s Disease Neuroimaging Initiative. 2018. Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer’s disease resilience. Genome Med 9(1):100.
Hohman TJ, Dumitrescu L, Barnes LL, Thambisetty M, Beecham G, Kunkle B, Gifford KA, Bush WS, Chibnik LB, Mukherjee S, De Jager PL, Kukull W, Crane PK, Resnick SM, Keene CD, Montine TJ, Schellenberg GD, Haines JL, Zetterberg H, Blennow K, Larson EB, Johnson SC, Albert M, Bennett DA, Schneider JA, Jefferson AL, Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Neuroimaging Initiative. 2018. Sex-specific association of Apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol 75(8):989–998.
Teslovich TM, Kim DS, Yin X, Stancáková A, Jackson AU, Wielscher M, Naj A, Perry JRB, Huyghe JR, Stringham HM, Davis JP, Raulerson CK, Welch RP, Fuchsberger C, Locke AE, Sim X, Chines PS, Narisu N, Kangas AJ, Soininen P; Genetics of Obesity-Related Liver Disease Consortium (GOLD), The Alzheimer’s Disease Genetics Consortium (ADGC), The DIAbetes Genetics Replication And Meta-analysis (DIAGRAM), Ala-Korpela M, Gudnason V, Musani SK, Jarvelin MR, Schellenberg GD, Speliotes EK, Kuusisto J, Collins FS, Boehnke M, Laakso M, Mohlke KL. 2018. Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study. Hum Mol Genet 27(9):1664–1674.
Chaudhury S, Patel T, Barber IS, Guetta-Baranes T, Brookes KJ, Chappell S, Turton J, Guerreiro RJ, Brás JM, Hernandez D, Singleton A, Hardy J, Mann D; ARUK Consortium, Morgan K. 2017. Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer’s disease. Neurobiol Aging 62:244.e1–244.e8.
Chang D, Nalls MA, Hallgrímsdóttir IB, Hunkapiller J, van der Brug M, Cai F, International Parkinson’s Disease Genomics Consortium, 23andMe Research Team, Kerchner GA, Ayalon G, Bingol B, Sheng M, Hinds D, Behrens TW, Singleton AB, Bhangale TR, Graham RR. 2017. A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat Genet 49(10):1511–1516.
Jansen IE, Gibbs JR, Nalls MA, Price TR, Lubbe S, van Rooij J, Uitterlinden AG, Kraaij R, Williams NM, Brice A, Hardy J, Wood NW, Morris HR, Gasser T, Singleton AB, Heutink P, Sharma, International Parkinson’s Disease Genomics Consortium. 2017. Establishing the role of rare coding variants in known Parkinson’s disease risk loci. Neurobiol Aging 59:220.e11–240.e18.
Darwent L, Carmona S, Lohmann E, Guven G, Kun-Rodrigues C, Bilgic B, Hanagasi H, Gurvit H, Erginel-Unaltuna N, Pak M, Hardy J, Singleton A, Brás JM, Guerreiro RJ. 2017. Mutations in TYROBP are not a common cause of dementia in a Turkish cohort. Neurobiol Aging 58:240.e1–240.e3.
Sims R … Brás JM, Guerreiro RJ … Schellenberg GD. 2017. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet 49(9):1373–1384.
Blauwendraat C, Faghri F, Pihlstrom L, Geiger JT, Elbaz A, Lesage S, Corvol JC, May P, Nicolas A, Abramzon Y, Murphy NA, Gibbs JR, Ryten M, Ferrari R, Brás JM, Guerreiro RJ, Williams J, Sims R, Lubbe S, Hernandez DG, Mok KY, Robak L, Campbell RH, Rogaeva E, Traynor BJ, Chia R, Chung SJ, International Parkinson’s Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium, Hardy JA, Brice A, Wood NW, Houlden H, Shulman JM, Morris HR, Gasser T, Krüger R, Heutink P, Sharma M, Simón-Sánchez J, Nalls MA, Singleton AB, Scholz SW. 2017. NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases. Neurobiol Aging 57:247.e13.
Ngoh A, Brás JM, Guerreiro RJ, McTague A, Ng J, Meyer E, Chong WK, Boyd S, MacLellan L, Kirkpatrick M, Kurian MA. 2017. BC1D24 mutations in a sibship with multifocal polymyoclonus. Tremor Other Hyperkinet Mov (NY) 7:452.
Siitonen M, Börjesson-Hanson A, Pöyhönen M, Ora A, Pasanen P, Brás JM, Kern S, Kern J, Andersen O, Stanescu H, Kleta R, Baumann M, Kalaria R, Kalimo H, Singleton A, Hardy J, Viitanen M, Myllykangas L, Guerreiro RJ. 2017. Multi-infarct dementia of Swedish type is caused by a 3’UTR mutation of COL4A1. Brain 140(5):e29.
Beesley C, Guerreiro RJ, Brás JM, Williams RE, Taratuto AL, Eltze C, Mole SE. 2016. CLN8 disease caused by large genomic deletions. Mol Genet Genomic Med 5(1):85–91.
Blauwendraat C, Nalls MA, Federoff M, Pletnikova O, Ding J, Letson C, Geiger JT, Gibbs JR, Hernandez DG, Troncoso JC, Simón-Sánchez J, Scholz SW, International Parkinson’s Disease Genomics Consortium. 2017. ADORA1 mutations are not a common cause of Parkinson’s disease and dementia with Lewy bodies. Mov Disord 32(2):298–299.
Barber IS, Braae A, Clement N, Patel T, Guetta-Baranes T, Brookes K, Medway C, Chappell S, Guerreiro RJ, Brás JM, Hernandez D, Singleton A, Hardy J, Mann DM, ARUK Consortium, Morgan K. 2017. Mutation analysis of sporadic early-onset Alzheimer’s disease using the NeuroX array. Neurobiol Aging 49:215.e1–215.e8.
Pasanen P, Mäkinen J, Myllykangas L, Guerreiro RJ, Brás JM, Valori M, Viitanen M, Baumann M, Tienari PJ, Pöyhönen M, Baumann P. 2017. Primary familial brain calcification linked to deletion of 5′ noncoding region of SLC20A2. Acta Neurol Scand 136(1):59–63.
Kun-Rodrigues C … Guerreiro RJ, Brás JM. 2017. Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies. 49:214.e13–215.e15.
Pottier C, Ravenscroft TA, Brown PH, Finch NA, Baker M, Parsons M, Asmann YW, Ren Y, Christopher E, Levitch D, van Blitterswijk M, Cruchaga C, Campion D, Nicolas G, Richard AC, Guerreiro RJ, Brás JM, Zuchner S, Gonzalez MA, Bu G, Younkin S, Knopman DS, Josephs KA, Parisi JE, Petersen RC, Ertekin-Taner N, Graff-Radford NR, Boeve BF, Dickson DW, Rademakers R. 2017. TYROBP genetic variants in early-onset Alzheimer’s disease. Neurbiol Aging 48:222.e1–222.e7.
Lubbe SJ, Escott-Price V, Brice A, Gasser T, Pittman AM, Bras J, Hardy J, Heutink P, Wood NM, Singleton AB, Grosset DG, Carroll CB, Law MH, Demenais F, Iles MM; Melanoma Meta-Analysis Consortium, Bishop DT, Newton-Bishop J, Williams NM, Morris HR, International Parkinson’s Disease Genomics Consortium. 2016. Rare variants analysis of cutaneous malignant melanoma genes in Parkinson’s disease. Neurobiol Aging 48:222.e1–222.e7.
Fountain MD, Aten E, Cho MT, Juusola J, Walkiewicz MA, Ray JW, Xia F, Yang Y, Graham BH, Bacino CA, Potocki L, van Haeringen A, Ruivenkamp CA, Mancias P, Northrup H, Kukolich MK, Weiss MM, van Ravenswaaij-Arts CM, Mathijssen IB, Levesque S, Meeks N, Rosenfeld JA, Lemke D, Hamosh A, Lewis SK, Race S, Stewart LL, Hay B, Lewis AM, Guerreiro RJ, Brás JM, Martins MP, Derksen-Lubsen G, Peeters E, Stumpel C, Stegmann S, Bok LA, Santen GW, Schaaf CP. 2017. The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families. Genet Med 19(1):45–52.
Lubbe SJ, Escott-Price V, Gibbs JR, Nalls MA, Brás JM, Price TR, Nicolas A, Jansen IE, Mok KY, Pittman AM, Tomkins JE, Lewis PA, Noyce AJ, Lesage S, Sharma M, Schiff ER, Levine AP, Brice A, Gasser T, Hardy J, Heutink P, Wood NW, Singleton AB, Williams NM, Morris HR; for International Parkinson’s Disease Genomics Consortium. 2016. Additional rare variant analysis in Parkinson’s disease cases with and without known pathogenic mutations: evidence for oligogenic inheritance. Hum Mol Genet 25(24):5483–5489.
Guven G, Lohmann E, Brás JM, Gibbs JR, Gurvit H, Bilgic B, Hanagasi H, Rizzu P, Heutink P, Emre M, Erginel-Unaltuna N, Just W, Hardy J, Singleton A, Guerreiro RJ. 2016. Mutation frequency of the major frontotemporal dementia genes, MAPT, GRN and C9ORF72 in a Turkish cohort of dementia patients. PLoS One 11(9):e0162592.
Brás JM, Djaldetti R, Alves AM, Mead S, Darwent L, Lleo A, Molinuevo JL, Blesa R, Singleton A, Hardy J, Clarimon J, Guerreiro RJ. 2016. Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer’s disease identifies a homozygous CTSF mutation. Neurobiol Aging 46:236.e1–6.
Guerreiro RJ, Brás JM, Batista S, Pires P, Ribeiro MH, Almeida MR, Oliveira C, Hardy J, Santana I. 2016. Pseudohypoparathyroidism type I-b with neurological involvement is associated with a homozygous PTH1R mutation. Genes Brain Behav 15(7):669–677.
Sassi C, Nalls MA, Ridge PG, Gibbs JR, Ding J, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C, Clement N, Lord J, Turton J, Brás JM, Almeida MR; ARUK Consortium, Holstege H, Louwersheimer E, van der Flier WM, Scheltens P, Van Swieten JC, Santana I, Oliveira C, Morgan K, Powell JF, Kauwe JS, Cruchaga C, Goate AM, Singleton AB, Guerreiro RJ, Hardy J. 2016. ABCA7 p.G215S as potential protective factor for Alzheimer’s disease. Neurobiol Aging 46:235e1–9.
Guerreiro RJ, Brown R, Dian D, de Goede C, Brás JM, Mole SE. 2016. Mutation of TBCK causes a rare recessive developmental disorder. Neurol Genet 2(3):e76.
Sassi C, Ridge PG, Nalls MA, Gibbs R, Ding J, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C, Lord J, Turton J; ARUK Consortium, Morgan K, Powell JF, Kauwe JS, Cruchaga C, Brás JM, Goate AM, Singleton AB, Guerreiro RJ, Hardy J. 2016. Influence of coding variability in APP-Aβ metabolism genes in sporadic Alzheimer’s disease. PLoS One 11(6):e0150079.
Ngoh A, Brás JM, Guerreiro RJ, Meyer E, McTague A, Dawson E, Mankad K, Gunny R, Clayton P, Mills PB, Thornton R, Lai M, Forsyth R, Kurian MA. 2016. RARS2 mutations in a sibship with infantile spasms. Epilepsia 57(5):e97–e102.
Ganos C, Crowe B, Stamelou M, Kresojević N, Lukić MJ, Brás JM, Guerreiro RJ, Taiwo F, Balint B, Batla A, Schneider SA, Erro R, Svetel M, Kostić V, Kurian MA, Bhatia KP. 2016. The clinical syndrome of dystonia with anarthria/aphonia. Parkinsonism Relat Disord 24:20–27.
Barber IS, García-Cárdenas JM, Sakdapanichkul C, Deacon C, Zapata Erazo G, Guerreiro RJ, Brás JM, Hernandez D, Singleton A, Guetta-Baranes T, Braae A, Clement N, Patel T, Brookes K, Medway C, Chappell S, Mann DM; ARUK Consortium, Morgan K. 2016. Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer’s disease. Neurobiol Aging 39:220.e1–7.
Lubbe SJ, Escott-Price V, Brice A, Gasser T, Hardy J, Heutink P, Sharma M, Wood NW, Nalls M, Singleton AB, Williams NM, Morris HR, International Parkinson’s Disease Genomics Consortium. 2016. Is the MC1R variant p.R160W associated with Parkinson’s? Ann Neurol 79(1):159–161.
Ryan NS, Nicholas JM, Weston PSJ, Liang Y, Lashley T, Guerreiro R, Adamson G, Kenny J, Beck J, Chavez-Gutierrez L, de Strooper B, Revesz T, Holton J, Mead S, Rossor MN, Fox NC. 2016. Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer’s disease: a case series. Lancet Neurol 15(13):1326–1335.
Jun G … Farrer LA. 2016. A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21(1):108–117.
Wang LS … Yu L. 2015. Rarity of the Alzheimer disease-protective APP A673T variant in the United States. JAMA Neurol 72(2):209–216.
Guerreiro RJ, Brás JM. 2015. The age factor in Alzheimer’s disease. Genome Med 7:106.
Kun-Rodrigues C, Ganos C, Guerreiro RJ, Schneider SA, Schulte C, Lesage S, Darwent L, Holmans P, Singleton A, International Parkinson’s Disease Genomics Consortium (IPDGC), Bhatia K, Brás JM. 2015. A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson’s disease. Hum Mol Genet 24(23):6711–6720.
Erro R, Hersheson J, Ganos C, Mencacci NE, Stamelou M, Batla A, Thust SC, Brás JM, Guerreiro RJ, Hardy J, Quinn NP, Houlden H, Bhatia KP. 2015. H-ABC syndrome and DYT4: Variable expressivity or pleiotropy of TUBB4 mutations? Mov Disord 30(6):828–833.
Brás JM, Alonso I, Barbot C, Costa MM, Darwent L, Orme T, Sequeiros J, Hardy J, Coutinho P, Guerreiro RJ. 2015. Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4. Am J Hum Genet 96(3):474–479.
Guerreiro RJ, Brás JM, Hardy J. 2015. SnapShot: Genetics of Parkinson’s disease. Cell 160(3):828–833.
Sassi C, Guerreiro RJ, Gibbs R, Ding J, Lupton MK, Troakes C, Al-Sarraj S, Niblock M, Gallo JM, Adnan J, Killick R, Brown KS, Medway C, Lord J, Turton J, Brás JM, Alzheimer’s Research UK Consortium, Morgan K, Powell JF, Singleton A, Hardy J. 2014. Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer’s disease. Neurobiol Aging 35(12):2881.e1–2881.e6.
Brás JM, Guerreiro RJ, Teo JTH, Darwent L, Vaughan J, Molloy S, Hardy J, Schneider SA. 2014. Atypical Parkinsonism-Dystonia Syndrome caused by a novel DJ1 mutation. Mov Disord 1(1):45–49.
Nalls MA … Singleton AB. 2014. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat Genet 46(9):989–893.
Guerreiro RJ, Brás JM, Wojtas A, Rademakers R, Hardy J, Graff-Radford N. 2014. Nonsense mutation in PRNP associated with clinical Alzheimer’s disease. Neurobiol Aging 35(11):2656.e13–2656.e16.
Sassi C, Guerreiro RJ, Gibbs R, Ding J, Lupton MK, Troakes C, Lunnon K, Al-Sarraj S, Brown KS, Medway C, Lord J, Turton J, Mann D, Snowden J, Neary D, Harris J, Brás JM, ARUK Consortium, Morgan K, Powell JF, Singleton A, Hardy J. 2014. Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer’s disease. Neurobiol Aging 35(10):2422.e13–16.
Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK, Kalia LV, Lobbestael E, Chia R, Ndukwe K, Ding J, Nalls MA, International Parkinson’s Disease Genomics Consortium, North American Brain Expression Consortium, Olszewski M, Hauser DN, Kumaran R, Lozano AM, Baekelandt V, Greene LE, Taymans JM, Greggio E, Cookson MR. 2014. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci U S A 111(7):2626–2631.
Benitez BA, Jin SC, Guerreiro RJ, Graham R, Lord J, Harold D, Sims R, Lambert JC, Gibbs JR, Brás JM, Sassi C, Harari O, Bertelsen S, Lupton MK, Powell J, Bellenguez C, Brown K, Medway C, Haddick PC, van der Brug MP, Bhangale T, Ortmann W, Behrens T, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD, Haines JL, Turton J, Braae A, Barber I, Fagan AM, Holtzman DM, Morris JC; 3C Study Group; EADI consortium; Alzheimer’s Disease Genetic Consortium (ADGC); Alzheimer’s Disease Neuroimaging Initiative (ADNI); GERAD Consortium, Williams J, Kauwe JS, Amouyel P, Morgan K, Singleton A, Hardy J, Goate AM, Cruchaga C. 2014. Missense variant in TREML2 protects against Alzheimer’s disease. Neurobiol Aging 35(6):1510.e19–26.
Cruchaga C, Karch CM, Jin SC, Benitez BA, Cai Y, Guerreiro RJ, Harari O, Norton J, Budde J, Bertelsen S, Jeng AT, Cooper B, Skorupa T, Carrell D, Levitch D, Hsu S, Choi J, Ryten M, Sassi C, Brás JM, Gibbs RJ, Hernandez DG, Lupton MK, Powell J, Forabosco P, Ridge PG, Corcoran CD, Tschanz JT, Norton MC, Munger RG, Schmutz C, Leary M, Demirci FY, Bamne MN, Wang X, Lopez OL, Ganguli M, Medway C, Turton J, Lord J, Braae A, Barber I, Brown K; Alzheimer’s Research UK (ARUK) Consortium, Pastor P, Lorenzo-Betancor O, Brkanac Z, Scott E, Topol E, Morgan K, Rogaeva E, Singleton A, Hardy J, Kamboh MI, George-Hyslop PS, Cairns N, Morris JC, Kauwe JSK, Goate AM. 2014. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease. Nature 505(7484):550–554.
Beecham GW … Alzheimer’s Disease Genetics Consortium (ADGC) … Montine TJ. 2014. Genome-wide association meta-analysis of neuropathologic features of Alzheimer’s disease and related dementias. PLoS Genet 10(9):e1004606.
Udayar V, Buggia-Prévot V, Guerreiro RL, Siegel G, Rambabu N, Soohoo AL, Ponnusamy M, Siegenthaler B, Bali J, AESG, Simons M, Ries J, Puthenveedu MA, Hardy J, Thinakaran G, Rajendran L. 2013. A paired RNAi and RabGAP overexpression screen identifies Rab11 as a regulator of β-amyloid production. Cell Rep 5(6):1536–1551.
Ahmed R, Guerreiro RJ, Rohrer JD, Guven G, Rossor MN, Hardy J, Fox NC. 2013. A novel A781V mutation in the CSF1R gene causes hereditary diffuse leucoencephalopathy with axonal spheroids. J Neurol Sci 332(1–2):141–144.
Guerreiro RJ, Brás JM, Hardy J. 2013. SnapShot: genetics of Alzheimer’s disease. Cell 155(4):968.
Holmans P, Moskvina V, Jones L, Sharma M, International Parkinson’s Disease Genomics Consortium, Vedernikov A, Buchel F, Saad M, Brás JM, Bettella F, Nicolaou N, Simón-Sánchez J, Mittag F, Gibbs JR, Schulte C, Durr A, Guerreiro RJ, Hernandez D, Brice A, Stefánsson H, Majamaa K, Gasser T, Heutink P, Wood NW, Martinez M, Singleton AB, Nalls MA, Hardy J, Morris HR, Williams NM. 2013. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson’s disease. Hum Mol Genet 22(5):1039–1049.
Moskvina V, Harold D, Russo G, Vedernikov A, Sharma M, Saad M, Holmans P, Brás JM, Bettella F, Keller MF, Nicolaou N, Simón-Sánchez J, Gibbs JR, Schulte C, Durr A, Guerreiro JR, Hernandez D, Brice A, Stefánsson H, Majamaa K, Gasser T, Heutink P, Wood N, Martinez M, Singleton AB, Nalls MA, Hardy J, Owen MJ, O’Donovan MC, Williams J, Morris HR, Williams NM, IPDGC and GERAD Investigators. 2013. Analysis of genome-wide association studies of Alzheimer disease and of Parkinson disease to determine if these 2 diseases share a common genetic risk. JAMA Neurol 70(10):1268–1276.
Guerreiro RJ, Lohmann E, Brás JM, Gibbs JR, Rohrer JD, Gurunlian N, Dursun B, Bilgic B, Hanagasi H, Gurvit H, Emre M, Singleton A, Hardy J. 2013. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol 70(1):78–84.
Guerreiro RJ, Bilgic B, Guven G, Brás JM, Rohrer J, Lohmann E, Hanagasi H, Gurvit H, Emre M. 2013. Novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family. Neurobiol Aging 34(12):2890ed.1–5.
Guerreiro RJ, Brás JM, Vieira M, Warrier V, Agrawal S, Stewart H, Anderson G, Mole SE. 2013. CLN6 disease caused by the same mutation originating in Pakistan has varying pathology. Eur J Paediatr Neurol 17(6):657–660.
Guerreiro RJ, Kara E, Le Ber I, Brás JM, Rohrer JD, Taipa R, Lashley T, Dupuits C, Gurunlian N, Mochel F, Warren JD, Hannequin D, Sedel F, Depienne C, Camuzat A, Golfier V, Du Boisguéheneuc F, Schottlaender L, Fox NC, Beck J, Mead S, Rossor MN, Hardy J, Revesz T, Brice A, Houlden H. 2013. Genetic analysis of inherited leukodystrophies: genotype-phenotype correlations in the CSF1R gene. JAMA Neurol 70(7):875–882.
Guerreiro RJ, Wojtas A, Brás JM, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J; Alzheimer Genetic Analysis Group. 2013. TREM2 variants in Alzheimer’s disease. N Engl J Med 368(2):117–127.
Keller MF, Saad M, Brás JM, Bettella F, Nicolaou N, Simón-Sánchez J, Mittag F, Büchel F, Sharma M, Gibbs JR, Schulte C, Moskvina V, Durr A, Holmans P, Kilarski LL, Guerreiro RJ, Hernandez DG, Brice A, Ylikotila P, Stefánsson H, Majamaa K, Morris HR, Williams N, Gasser T, Heutink P, Wood NW, Hardy J, Martinez M, Singleton AB, Nalls MA; International Parkinson’s Disease Genomics Consortium (IPDGC); Wellcome Trust Case Control Consortium 2 (WTCCC2). 2013. Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinson’s disease. Hum Mol Genet 21(22):4996–5009.
Charlesworth G, Gandhi S, Brás JM, Barker RA, Burn DJ, Chinnery PF, Gentleman SM, Guerreiro RJ, Hardy J, Holton JL, Lees A, Morrison K, Sheerin UM, Williams N, Morris H, Revesz T, Wood NW. 2012. Tau acts as an independent genetic risk factor in pathologically proven PD. Neurobiol Aging 33(4):838.e7–11.
Guerreiro RJ, Lohmann E, Kinsella E, Brás JM, Luu N, Gurunlian N, Dursun B, Bilgic B, Santana I, Hanagasi H, Gurvit H, Gibbs JR, Oliveira C, Emre M, Singleton A. 2012. Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer’s disease. Neurobiol Aging 33(5):1008.e1–23.
Brás JM, Guerreiro RJ, Hardy J. 2012. Use of next-generation sequencing and other whole-genome strategies to dissect neurological disease. Nat Rev Neurosci 13(7):453–464.
Guerreiro RJ, Lohmann E, Kinsella E, Brás JM, Luu N, Gurunlian N, Dursun B, Bilgic B, Santana I, Hanagasi H, Gurvit H, Gibbs JR, Oliveira C, Emre M, Singleton A. 2012. Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer’s disease. Neurobiol Aging 33(5):1008.e17–23.
Guerreiro RJ, Baquero M, Blesa R, Boada M, Brás JM, Bullido MJ, Calado A, Crook R, Ferreira C, Frank A, Gómez-Isla T, Hernández I, Lleó A, Machado A, Martínez-Lage P, Masdeu J, Molina-Porcel L, Molinuevo JL, Pastor P, Pérez-Tur J, Relvas R, Oliveira CR, Ribeiro MH, Rogaeva E, Sa A, Samaranch L, Sánchez-Valle R, Santana I, Tàrraga L, Valdivieso F, Singleton A, Hardy J, Clarimón J. 2010. Genetic screening of Alzheimer’s disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging 31(5):725–731.
Nalls MA, Guerreiro RJ, Simon-Sanchez J, Brás JM, Traynor BJ, Gibbs JR, Launer L, Hardy J, Singleton AB. 2009. Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer’s disease. Neurogenetics 10(3):183–190.
Brás JM, Paisan-Ruiz C, Guerreiro RJ, Ribeiro MH, Morgadinho A, Januario C, Sidransky E, Oliveira C, Singleton A. 2009. Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Portugal. Neurobiol Aging 30(9):1515–1517.
Guerreiro RJ, Santana I, Brás JM, Revesz T, Rebelo O, Ribeiro MH, Santiago B, Oliveira CR, Singleton A, Hardy J. 2008. Novel progranulin mutation: screening for PGRN mutations in a Portuguese series of FTD/CBS cases. Mov Disord 23(9):1699–1673.
Jakobsson M, Scholz SW, Scheet P, Gibbs JR, VanLiere JM, Fung HC, Szpiech ZA, Degnan JH, Wang K, Guerreiro RJ, Brás JM, Schymick JC, Hernandez DG, Traynor BJ, Simon-Sanchez J, Matarin M, Britton A, van de Leemput J, Rafferty I, Bucan M, Cann HM, Hardy JA, Rosenberg NA, Singleton AB. 2008. Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451(7181):998–1003.
Camargos S, Scholz S, Simón-Sánchez J, Paisán-Ruiz C, Lewis P, Hernandez D, Ding J, Gibbs JR, Cookson MR, Brás JM, Guerreiro RJ, Oliveira CR, Lees A, Hardy J, Cardoso F, Singleton AB. 2008. DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA. Lancet Neurol 7(3):207–215.
Guerreiro RJ, Santana I, Brás JM, Santiago B, Paiva A, Oliveira C. 2007. Peripheral inflammatory cytokines as biomarkers in Alzheimer’s disease and mild cognitive impairment. Neurodegener Dis 4(6):406–412.
Guerreiro RJ, Brás JM, Santana I, Januario C, Santiago B, Morgadinho AS, Ribeiro MH, Hardy J, Singleton A, Oliveira C. 2006. Association of HFE common mutations with Parkinson’s disease, Alzheimer’s disease and mild cognitive impairment in a Portuguese cohort. BMC Neurol 6:24.
Brás JM, Guerreiro RJ, Ribeiro MH, Januario C, Morgadinho A, Oliveira CR, Cunha L, Hardy J, Singleton A. 2005. G2019S dardarin substitution is a common cause of Parkinson’s disease in a Portuguese cohort. Mov Disord 20(12):1652–1655.
Nadia Dehghani, B.Sc.
Ph.D. Candidate, VAI Graduate School
Thesis: Genetic characterization of dementia in a Turkish cohort
Jamie Durst, B.S.
Senior Administrative Assistant I, Department of Neurodegenerative Science
Mehrshid Faraji Zonooz
Ph.D. Candidate, VAI Graduate School
Thesis project title to be determined
Kimberly Paquette, B.A.
Laboratory Project Specialist I, Department of Neurodegenerative Science
Andrew Pyman
Assistant Research Technician, Department of Neurodegenerative Science
Kaitlyn Westra, B.S.
Computational Biologist I, Department of Neurodegenerative Science
