Ongoing Research Projects 

1.    The GENetic Frontotemporal Dementia Initiative (GENFI): a new multi-centre platform for the study of frontotemporal lobar degeneration (2015-Present)

2.    The neuroinflamatory reaction to acute systemic inflammation during delirium and its impact in the cognitive trajectory and progression to dementia: a case-control longitudinal study using imaging and molecular biomarkers - POCI-01-0145-FEDER-032501 (2018-2021)

3.    Beyond Beta-Amyloid - Deciphering Early Pathogenic Changes in Alzheimer's Disease -  PTDC/MED-NEU/27946/2017 (2018-2021)

4.    Affective disorders: biomarkers and early detection POCI-01-0145-FEDER-30943 (2018-2021)

5.    Alemtuzumab therapy in Multiple Sclerosis: tracking immune cell trafficking, induced molecular mechanisms and aftermath effects - GZ-2017-11730 (2019 – 2022)

6.    BrEin-MS — Brain Elasticity in Multiple Sclerosis and implications in mechanomodulation of oligodendrocytes: a cellular and clinical approach - PTDC/MED-NEU/29516/2017 (2018-2021)

7.    BioMuScle - Novos biomarcadores de imagem multimodal de conectividade neuronal na Esclerose Múltipla - PTDC/MEC-NEU/31973/2017 (2018-2021)

External collaborations 

1.    Rita Guerreiro, José Miguel Brás - Van Andel Institute, Grand Rapids, Michigan, USA - https://guerreirolab.vai.org/

2.    GENFI – Genetic Frontotemporal Dementia Initiative - Dementia Research Center, University College London (UCL), UK - https://www.ucl.ac.uk/drc/research-studies/genfi

3.    Franc Llorens - Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III (ISCIII), L’Hospitalet de Llobregat, Spain.

4.    Inga Zerr - Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical School, Göttingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany

5.    Peter Jielle Visser - Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands

6.    Christine Van Broeckhoven,  EU EOD Consortium (European Early-Onset Dementia Consortium) - VIB Center for Molecular Neurology, Antwerpen, Belgium

7.    EADC - European Alzheimer’s Disease Consortium

Our main focus is the identification of new biomarkers for brain diseases, leading to an accurate and early diagnosis to improve patient management and promoting the design of patient-tailored preventive and therapeutic interventions. 

We aim to identify biological markers that specifically reflect the onset of pathology in patients with neurological and neuropsychiatric diseases. Assay platforms will be developed as tools to elucidate the unsolved clinical, genetic and pathological heterogeneity observed in these disorders that seriously affect the efficacy and outcome of clinical trials.

Both targeted and “OMICS” methodologies will be applied (in close collaboration with the Life Sciences Mass Spectrometry group), under a translational perspective, to the study of brain disorders, generating tools for diagnosis, prognosis and progression markers, crucial for planning patient’s assistance and management of economic resources.

The team members work in different locations, namely Centro Hospitalar e Universitário de Coimbra (CHUC) and Faculty of Medicine (Polo III). Available resources include: Single Molecule Array (SiMoA) SR-X platform, manual and fully automated immunoassay equipments, HPLC apparatus, Thermocyclers, DNA automated sequencer (Beckman-Coulter) and MiSeq platform (Illumina).

The research developed in the group relies on collaborative efforts between fundamental researchers and clinicians for access to human biological samples and clinical data. The team is integrated in quality control programs and international consortia that defines standard methodologies for sample collection, data analysis and information storage.

Keywords

Neurological diseases

Neuropsychiatric diseases

Diagnosis 

Biomarkers

Research Lines 

1 - Deciphering Early Pathogenic Changes in Neurodegenerative Dementias 
2 - Monitoring disease-modifying therapy in Multiple Sclerosis 
3 - Identification of genetic and biochemical markers underpinning mechanisms in cerebral small vessel disease
4 - Affective disorders: biomarkers and early detection (coordinated by the Life Sciences Mass Spectrometry group)

Selected Publications

1.    Llorens, Franc; Hermann, Peter; Villar-Pique, Anna; Diaz-Lucena, Daniela; Nagga, Katarina; Hansson, Oskar; Santana, Isabel; Schmitz, Matthias; Schmidt, Christian; Varges, Daniela; Goebel, Stefan; Dumurgier, Julien; Zetterberg, Henrik; Blennow, Kaj; Paquet, Claire; Baldeiras, Ines; Ferrer, Isidro; Zerr, Inga. Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia. Nature communications, 2020, 11, 619‒. DOI: 10.1038/s41467-020-14373-2.

2.    Silva, Dina; Cardoso, Sandra; Guerreiro, Manuela; Maroco, Joao; Mendes, Tiago; Alves, Luisa; Nogueira, Joana; Baldeiras, Ines; Santana, Isabel; de Mendonca, Alexandre. Neuropsychological Contribution to Predict Conversion to Dementia in Patients with Mild Cognitive Impairment Due to Alzheimer's Disease. JOURNAL OF ALZHEIMERS DISEASE, 2020, 74, 785‒796. DOI: 10.3233/JAD-191133.

3.    van der Ende, Emma L.; Meeter, Lieke H.; Poos, Jackie M.; Panman, Jessica L.; Jiskoot, Lize C.; Dopper, Elise G. P.; Papma, Janne M.; de Jong, Frank Jan; Verberk, Inge M. W.; Teunissen, Charlotte; Rizopoulos, Dimitris; Heller, Carolin; Convery, Rhian S.; Moore, Katrina M.; Bocchetta, Martina; Neason, Mollie; Cash, David M.; Borroni, Barbara; Galimberti, Daniela; Sanchez-Valle, Raquel; Laforce, Robert, Jr.; Moreno, Fermin; Synofzik, Matthis; Graff, Caroline; Cash, David M.; Borroni, Barbara; Galimberti, Daniela; Sanchez-Valle, Raquel; Laforce, Robert, Jr.; Moreno, Fermin; Synofzik, Matthis; Graff, Caroline; Masellis, Mario; Tartaglia, Maria Carmela; Rowe, James B.; Vandenberghe, Rik; Finger, Elizabeth; Tagliavini, Fabrizio; de Mendonca, Alexandre; Santana, Isabel; Butler, Chris; Ducharme, Simon; Gerhard, Alex; Danek, Adrian; Levin, Johannes; Otto, Markus; Frisoni, Giovanni B.; Cappa, Stefano; Pijnenburg, Yolande A. L.; Rohrer, Jonathan D.; van Swieten, John C. and the Genetic Frontotemporal Dementia Initiative (GENFI). Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study. LANCET NEUROLOGY, 2019, 18, 1103‒1111. DOI: N/A.

4.    Healey, Jeff S.; Gladstone, David J.; Swaminathan, Balakumar; Eckstein, Jens; Mundl, Hardi; Epstein, Andrew E.; Haeusler, Karl Georg; Mikulik, Robert; Kasner, Scott E.; Toni, Danilo; Arauz, Antonio; Ntaios, George; Hankey, Graeme J.; Perera, Kanjana; Pagola, Jorge; Shuaib, Ashfaq; Lutsep, Helmi; Yang, Xiaomeng; Uchiyama, Shinichiro; Endres, Matthias; Coutts, Shelagh B.; Karlinski, Michal; Czlonkowska, Anna; Molina, Carlos A.; Santo, Gustavo; Berkowitz, Scott D.; Hart, Robert G.; Connolly, Stuart J.. Recurrent Stroke With Rivaroxaban Compared With Aspirin According to Predictors of Atrial Fibrillation Secondary Analysis of the NAVIGATE ESUS Randomized Clinical Trial. JAMA NEUROLOGY, 2019, 76, 764‒773. DOI: 10.1001/jamaneurol.2019.0617

5.    van Maurik, Ingrid S.; Vos, Stephanie J.; Bos, Isabelle; Bouwman, Femke H.; Teunissen, Charlotte E.; Scheitens, Philip; Barkhof, Frederik; Frolich, Lutz; Kornhuber, Johannes; Wiftfang, Jens; Maier, Wolfgang; Peters, Oliver; ROther, Eckart; Nobili, Flavio; Frisoni, Giovanni B.; Spiru, Luiza; Freund-Levi, Yvonne; Wallin, Asa K.; Hampel, Harald; Soininen, Hilkka; Tsolaki, Magda; Verhey, Frans; Kloszewska, Iwona; Mecocci, Patrizia; Vellas, Bruno; Lovestone, Simon; Gailuzzi, Samantha; Herukka, Sanna-Kaisa; Santana, Isabel; Baldeiras, Ines; de Mendonca, Alexandre; Silva, Dina; Chetelat, Gael; Egret, Stephanie; Palmqvist, Sebastian; Hansson, Oskar; Visser, Pieter Jelle; Berkhof, Johannes; van der Flier, Wiesje M. Alzheimer's Disease Neuroimaging Initiative. Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study. LANCET NEUROLOGY, 2019, 18, 1034‒1044. DOI: 10.1016/S1474-4422(19)30283-2.

6.    Letra, Liliana; Rodrigues, Tiago; Matafome, Paulo; Santana, Isabel; Seica, Raquel. Adiponectin and sporadic Alzheimer's disease: Clinical and molecular links. FRONTIERS IN NEUROENDOCRINOLOGY, 2019, 52, 1‒11. DOI: 10.1016/j.yfrne.2017.10.002 

7.    Santana I, Baldeiras I, Santiago B, Duro D, Freitas S, Tábuas-Pereira M, AlmeidaMR, Oliveira CR. Underlying biological processes in Mild Cognitive Impairment: amyloidosis versus neurodegeneration. J Alzheimers Dis. 2018; 64(s1):S647-S657. DOI: 10.3233/JAD-179908.

8.    Zerr I, Schmitz M, Karch A, Villar-Piqué A, Kanata E, Golanska E, Díaz-Lucena D, Karsanidou A, Hermann P, Knipper T, Goebel S, Varges D, Sklaviadis T, Sikorska B, Liberski PP, Santana I, Ferrer I, Zetterberg H, Blennow K, Calero O, Calero M, Ladogana A, Sánchez-Valle R, Baldeiras I, Llorens F. Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases. Alzheimers & Dement. 2018;14:751-763. DOI: 10.1016/j.jalz.2017.12.008.

9.    Baldeiras I, Santana I, Leitão MJ, Gens H, Pascoal R, Tábuas-Pereira M, Beato-Coelho J, Duro D, Almeida MR, Oliveira CR. Addition of the Aβ42/40 ratio to the Cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in Mild Cognitive Impairment. Alzheimer's Res & Ther 2018;18:30. DOI: 10.1186/s13195-018-0362-2

10.    Jansen, Willemijn J.; Ossenkoppele, Rik; Tijms, Betty M.; Fagan, Anne M.; Hansson, Oskar; Klunk, William E.; van der Flier, Wiesje M.; Villemagne, Victor L.; Frisoni, Giovanni B.; Fleisher, Adam S.; Lleo, Alberto; Mintun, Mark A.; Wallin, Anders; Engelborghs, Sebastiaan; Na, Duk L.; Chetelat, Gael; Molinuevo, Jose Luis; Landau, Susan M.; Mattsson, Niklas; Kornhuber, Johannes; Sabri, Osama; Rowe, Christopher C.; Parnetti, Lucilla; Popp, Julius; Fladby, Tormod; Jagust, William J.; Aalten, Pauline; Lee, Dong Young; Vandenberghe, Rik; de Oliveira, Catarina Resende; Kapaki, Elisabeth; Froelich, Lutz; Ivanoiu, Adrian; Gabryelewicz, Tomasz; Verbeek, Marcel M.; Sanchez-Juan, Pascual; Hildebrandt, Helmut; Camus, Vincent; Zboch, Marzena; Brooks, David J.; Drzezga, Alexander; Rinne, Juha O.; Newberg, Andrew; de Mendonca, Alexandre; Sarazin, Marie; Rabinovici, Gil D.; Madsen, Karine; Kramberger, Milica G.; Nordberg, Agneta; Mok, Vincent; Mroczko, Barbara; Wolk, David A.; Meyer, Philipp T.; Tsolaki, Magda; Scheltens, Philip; Verhey, Frans R. J.; Visser, Pieter Jelle and the Amyloid Biomarker Study Group. Association of Cerebral Amyloid-beta Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA PSYCHIATRY, 2018, 75, 84‒95. DOI: 10.1001/jamapsychiatry.2017.3391

11.    Guerreiro, Rita; Ross, Owen A.; Kun-Rodrigues, Celia; Hernandez, Dena G.; Orme, Tatiana; Eicher, John D.; Shepherd, Claire E.; Parkkinen, Laura; Darwent, Lee; Heckman, Michael G.; Scholz, Sonja W.; Troncoso, Juan C.; Pletnikova, Olga; Ansorge, Olaf; Clarimon, Jordi; Lleo, Alberto; Morenas-Rodriguez, Estrella; Clark, Lorraine; Honig, Lawrence S.; Marder, Karen; Lemstra, Afina; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Holton, Janice; Compta, Yaroslau; Van Deerlin, Vivianna; Serrano, Geidy E.; Beach, Thomas G.; Lesage, Suzanne; Galasko, Douglas; Masliah, Eliezer; Santana, Isabel; Pastor, Pau; Diez-Fairen, Monica; Aguilar, Miquel; Tienari, Pentti J.; Myllykangas, Liisa; Oinas, Minna; Revesz, Tamas; Lees, Andrew; Boeve, Brad F.; Petersen, Ronald C.; Ferman, Tanis J.; Escott-Price, Valentina; Graff-Radford, Neill; Cairns, Nigel J.; Morris, John C.; Pickering-Brown, Stuart; Mann, David; Halliday, Glenda M.; Hardy, John; Trojanowski, John Q.; Dickson, Dennis W.; Singleton, Andrew; Stone, David J.; Bras, Jose. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. LANCET NEUROLOGY, 2018, 17, 64‒74. DOI: 10.1016/S1474-4422(17)30400-3.
​
12.    Disconnection as a mechanism for social cognition impairment in multiple sclerosis. Batista S, Alves C, d'Almeida OC, Afonso A, Félix-Morais R, Pereira J, Macário C, Sousa L, Castelo-Branco M, Santana I, Cunha L. Neurology. 2017 Jul 4;89(1):38-45. DOI: 10.1212/WNL.0000000000004060.