WORK PACKAGE 8

Clinical studies

Twelve INMiND partner institutions from ten countries (Belgium, Denmark, Finland, France, Germany, Italy, Sweden, The Netherlands, United Kingdom) are involved in the research activities of this work package. Leader of this work package is Alexander GERHARD from the Wolfson Molecular Imaging Centre (WMIC) at the University of Manchester (United Kingdom).

The main objectives of this work package are:

  • to evaluate new tracers for microglial activation

  • to haracterise the role of microglial activation with in vivo imaging in selected human neurodegenerative disorders

  • to study non-ND disorders yielding complementary information on the in vivo assessment of NI that are of relevance for ND

  • to assess reactive astrocytosis in NI alongside with microglial activation

WP8 Related papers


Epub ahead of print

Chiotis K,  Saint-Aubert L, Rodriguez-Vieitez E, Leuzy A, Almkvist O, Savitcheva I, Jonasson M, Lubberink M, Wall A, Antoni G, Nordberg A. Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal  and Alzheimer disease dementia. Mol Psychiatry. 2017; epub ahead of print.
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Marchitelli R, Aiello M, Cachia A, Quarantelli M, Cavaliere C, Postiglione A, Tedeschi G, Montella P, Milan G, Salvatore M, Salvatore E, Baron JC, Pappatà S. Simultaneous resting-state FDG-PET/fMRI in Alzheimer Disease: Relationship between glucose metabolism and intrinsic activity. Neuroimage. 2018 Apr 27;176:246-258; epub ahead of print.
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2018

Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS. Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study. Biol Psychiatry. 2018;83(1):61-69.
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Leuzy A, Rodriguez-Vieitez E, Saint-Aubert L, Chiotis K, Almkvist O, Savitcheva I, Jonasson M, Lubberink M, Wall A, Antoni G, Nordberg A. Longitudinal uncoupling of cerebral perfusion, glucose metabolism and tau deposition in Alzheimer’s disease. Alzheimers Dement. 2018;14(5):652-663.
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Pilotto A, Premi E, Caminiti SP, Presotto L, Alberici A, Paghera B, Borroni B, Padovani A, Perani D. Single-subject SPM FDG-PET patterns predict risk of dementia progression in Parkinson disease. Neurology. 2018 Mar 20;90(12):e1029-e1037.
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Rissanen E, Tuisku J, Vahlberg T, Sucksdorff M, Paavilainen T, Parkkola R, Rokka J, Gerhard A, Hinz R, Talbot PS, Rinne JO, Airas L. Microglial activation, white matter tract damage, and disability in MS. Neurol Neuroimmunol Neuroinflamm. 2018;5(3):e443.
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Veronese M, Reis Marques T, Bloomfield PS, Rizzo G, Singh N, Jones D, Agushi E, Mosses D, Bertoldo A, Howes O, Roncaroli F, Turkheimer FE. Kinetic modelling of [11C]PBR28 for 18 kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis. J Cereb Blood Flow Metab. 2018;38(7):1227-1242.
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2017

Airas L, Rissanen E, Rinne J. Imaging of microglial activation in MS using PET: Research use and potential future clinical application. Mult Scler. 2017;23(4):496-504.
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Caminiti SP, Presotto L, Baroncini D, Garibotto V, Moresco RM, Gianolli L, Volonté MA, Antonini A, Perani D. Axonal damage and loss of connectivity in nigrostriatal and mesolimbic dopamine pathways in early Parkinson's disease. Neuroimage Clin. 2017;14:734-740.
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Caminiti SP, Tettamanti M, Sala A, Presotto L, Iannaccone S, Cappa SF, Magnani G and Perani D; Alzheimer’s Disease Neuroimaging Initiative (ADNI). Metabolic connectomics targeting brain pathology in dementia with Lewy bodies. J Cereb Blood Flow Metab. 2017;37(4):1311-1325.
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Cerami C, Iaccarino L, Perani D. Molecular imaging of neuroinflammation in neurodegenerative dementias: The role of in vivo PET imaging. Int J Mol Sci. 2017;18(5).
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Collste K, Plavén-Sigray P, Fatouros-Bergman H, Victorsson P, Schain M, Forsberg A, Amini N, Aeinehband S; Karolinska Schizophrenia Project (KaSP) consortium., Erhardt S, Halldin C, Flyckt L, Farde L, Cervenka S. Lower levels of the glial cell marker TSPO in drug-naïve first episode psychosis patients as measured using PET and [11C]PBR28. Mol Psychiatry. 2017;22(6):850-856.
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Dupont AC, Largeau B, Santiago Ribeiro MJ, Guilloteau D, Tronel C, Arlicot N. Translocator protein-18kDa (TSPO) positron emision tomography (PET) imaging and it clinical impact in neurodegenerative diseases. Int J Mol Sci. 2017;18(4):785.
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Forsberg A, Cervenka S, Jonsson Fagerlund M, Rasmussen LS, Zetterberg H, Erlandsson Harris H, Stridh P, Christensson E, Granström A, Schening A, Dymmel K, Knave N, Terrando N, Maze M, Borg J, Varrone A, Halldin C, Blennow K, Farde L, Eriksson LI. The immune response of the human brain to abdominal surgery. Ann Neurol. 2017;81(4):572-582.
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Iaccarino L, Chiotis K, Alongi P, Almkvist O, Wall A, Cerami C, Bettinardi V, Gianolli L, Nordberg A, Perani D. A cross-validation of FDG- and amyloid-PET biomarkers inmild cognitive impairment for the risk prediction to dementia due to Alzheimer's Disease in a clinical setting. J Alzheimers Dis. 2017;59(2):603-614.
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Lemoine L, Gillberg P-G, Svedberg M, Stepanov CV, Jia Z, Huang J, Nag S, Tian H, Ghetti B, Okamura N, Higuchi M,  Halldin C, Nordberg A. Comparative binding properties of the tau PET tracers THK5117, THK5351, PBB3, and T807 in postmortem Alzheimer brains. Alzheimers Res Ther. 2017;9(1):96.
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Lemoine L, Saint-Aubert L, Nennesmo I, Gillberg P-G, Nordbrerg A. Cortical laminar tau deposit and activated astrocytes in Alzheimer´s disease visualized by 3H-THK5117 and 3H-deprenyl autoradiography. Sci Rep 2017;7:45496.
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Ni R, Gillberg PG, Bogdanovic N, Viitanen M, Myllykangas L, Nennesmo I, Långström B, Nordberg A. Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease. Alzheimers Dement. 2017;13(4):419-430.
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Perani D, Farsad M, Ballarini T, Lubian F, Malpetti M, Fracchetti A, Magnani G, March A, Abutalebi J. The impact of bilingualism on brain reserve and metabolic connectivity in Alzheimer's dementia. Proc Natl Acad Sci U S A. 2017;114(7):1690-1695.
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Presotto L, Ballarini T, Caminiti SP, Bettinardi V, Gianolli L, Perani D. Validation of 18F–FDG-PET Single-Subject Optimized SPM Procedure with Different PET Scanners. Neuroinformatics. 2017;15(2):151-163.
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Rodriguez-Vieitez E, Leuzy A, Chiotis K, Saint-Aubert, Wall A, Nordberg A. Comparability of [18F]THK5317 and [11C]PIB blood flow proxy images with [18F]FDG positron emission tomography in Alzheimer's disease. J Cereb Blood Flow Metab. 2017;37(2):740-749.
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Saint-Aubert L, Lemoine L, Chiotis K, Leuzy A, Rodriguez-Vieitez E, Nordberg A. Tau PET imaging: present and future directions. Mol Neurodegener. 2017;12(1):19.
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Sala A, Caminiti SP, Presotto L, Premi E, Pilotto A, Turrone R, Cosseddu M, Alberici A, Paghera B, Borroni B, Padovani A, Perani D. Sci Rep. 2017;7(1):4256.
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Sucksdorff M, Rissanen E, Tuisku J, Nuutinen S, Paavilainen T, Rokka J, Rinne J, Airas L. Evaluation of the effect of Fingolimod treatment on microglial activation using serial PET imaging in multiple sclerosis. J Nucl Med. 2017;58(10):1646-1651.
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Tronel C, Largeau B, Santiago Ribeiro MJ, Guilloteau D, Dupont AC, Arlicot N. Molecular targets for PET imaging of activated microglia: the current situation and future expectations. Int J Mol Sci. 2017;18(4):802.
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Van der Aart J, van der Doef TF, Horstman P, Schuit RC, van Lingen A, Windhorst AD, van Berckel BNM, Lammertsma AA. Human Dosimetry of the NMDA Receptor Ligand [11C]GMOM. J Nucl Med. 2017;58(8):1330-1333.
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2016

Cerami C, Dodich A, Greco L, Iannaccone S, Magnani G, Marcone A, Pelagallo E, Santangelo R, Cappa SF, Perani D. The role of single-subject brain metabolic patterns in the early differential diagnosis of primary progressive aphasias and in prediction of progression to dementia. J Alzheimers Dis. 2016;55(1):183-197.
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Cerami C, Dodich A, Lettieri G, Iannaccone S, Magnani G, Marcone A, Gianolli L, Cappa SF, Perani D. Different FDG-PET metabolic patterns at single-subject level in the behavioral variant of fronto-temporal dementia. Cortex. 2016;83:101-12.
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Chiotis K, Saint-Aubert L, Savitcheva I, Jelic V, Andersen P, Jonasson M, Eriksson J, Lubberink M, Almkvist O, Wall A, Antoni G, Nordberg A. Imaging in-vivo tau pathology in Alzheimer’s disease with THK5317 PET in a multimodal paradigm. Eur J Nucl Med Mol Imaging. 2016;43(9):1686-99.
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Collste K, Forsberg A, Varrone A, Amini N, Aeinehband S, Yakushev I, Halldin C, Farde L, Cervenka S. Test-retest reproducibility of [11C]PBR28 binding to TSPO in healthy control subjects. Eur J Nucl Med Mol Imaging. 2016 Jan;43(1):173-83.
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Dupont AC, Guilloteau D, Kassiou M, Ribeiro MJ, Vercouillie J, Katsifis A, Arlicot N. Radiopharmaceuticals for PET imaging of neuroinflammation - Les radiopharmaceutiques pour l’imagerie TEP de la neuroinflammation. Médecine Nucléaire. 2016;40(1):72-81.
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Gerhard A. TSPO imaging in parkinsonian disorders. Clin Transl Imaging. 2016;4:183-190.
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Gerhard A. In-vivo-Bildgebung „neuroinflammatorischer Veränderungen“ mit PET; Grundlagen und Anwendung bei Parkinson-Syndromen. Nuklearmediziner 2016;39(04):309-315.
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Golla SS, Boellaard R, Oikonen V, Hoffmann A, van Berckel BN, Windhorst AD, Virta J, Te Beek ET, Groeneveld GJ, Haaparanta-Solin M, Luoto P, Savisto N, Solin O, Valencia R, Thiele A, Eriksson J, Schuit RC, Lammertsma AA, Rinne J. Parametric binding images of the TSPO ligand [18F]DPA-714. J Nucl Med. 2016;57(10):1543-1547.
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Hamelin L, Lagarde J, Dorothée G, Leroy C, Labit M, Comley RA, de Souza LC, Corne H, Dauphinot L, Bertoux M, Dubois B, Gervais P, Colliot O, Potier MC, Bottlaender M, Sarazin M; Clinical IMABio3 team. Early and protective microglial activation in Alzheimer's disease: a prospective study using 18F-DPA-714 PET imaging. Brain. 2016;139(Pt 4):1252-64.
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Holmes SE, Hinz R, Drake RJ, Gregory CJ, Conen S, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS. In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study. Mol Psychiatry. 2016;21(12):1672-1679.
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Jonasson M, Wall A, Chiotis K, Saint-Aubert L, Wilking H, Sprycha M, Borg B, Thibblin A, Eriksson JP, Sörensen J, Antoni G, Nordberg A, Lubberink M. Tracer kinetic analysis of (S)-18F-THK5117 as a PET tracer for assessing tau pathology. J Nucl Med. 2016;57(4):574-81.
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Kanegawa N, Collste K, Forsberg A, Schain M, Arakawa R, Jucaite A, Lekander M, Olgart Höglund C, Kosek E, Lampa J, Halldin C, Farde L, Varrone A, Cervenka S. In vivo evidence of a functional association between immune cells in blood and brain in healthy human subjects. Brain Behav Immun. 2016;54:149-57.
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Kumar R, Nordberg A, Darreh-Shori T. Amyloid-β peptides act as allosteric modulators of cholinergic signalling through formation of soluble BAβACs. Brain. 2016;139(Pt 1):174-92.
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Leuzy A, Chiotis K, Hasselbalch SG, Rinne JO, de Mendonça A, Otto M, Lleó A, Castelo-Branco M, Santana I, Johansson J, Anderl-Straub S, von Arnim CA, Beer A, Blesa R, Fortea J, Herukka SK, Portelius E, Pannee J, Zetterberg H, Blennow K, Nordberg A. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study. Brain. 2016;139(Pt 9):2540-53.
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Perani D, Cerami C, Caminiti SP, Santangelo R, Coppi E, Ferrari L, Pinto P, Passerini G, Falini A, Iannaccone S, Cappa SF, Comi G, Gianolli L,  Magnani G. Cross-validation of biomarkers to early differential diagnosis and prognosis of dementia in a clinical setting. Eur J Nucl Med Mol Imaging. 2016;43(3):499-508.
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Rodriguez-Vieitez E, Carter SF, Chiotis K, Saint-Aubert L, Leuzy A, Schöll M, Almkvist O, Wall A, Långström B, Nordberg A. Comparison of Early-Phase 11C-Deuterium-L-Deprenyl and 11C-PiB PET for Assessing Brain Perfusion in Alzheimer's Disease. J Nucl Med. 2016;57(7):1071-7.
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Rodriguez-Vieitez E, Saint-Aubert L, Carter SF, Almkvist O, Farid K, Schöll M, Chiotis K, Thordardottir S, Graff C, Wall A, Långström B, Nordberg A. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease. Brain. 2016;139(Pt 3):922-36.
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Roncaroli F, Su Z, Herholz K, Gerhard A, Turkheimer FE. TSPO expression in brain tumours: is TSPO a target for brain tumour imaging? Clin Transl Imaging. 2016;4(2):145-156.
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Ruffmann C, Calboli FC, Bravi I, Gveric D, Curry LK, de Smith A, Pavlou S, Buxton JL, Blakemore AI, Takousis P, Molloy S, Piccini P, Dexter DT, Roncaroli F, Gentleman SM, Middleton LT. Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases. Neuropathol Appl Neurobiol. 2016;42(5):436-50.
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Saint-Aubert L, Almkvist O, Chiotis K, Almeida R, Wall A, Nordberg A. Regional tau deposition measured by [18F]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer's disease. Alzheimers Res Ther. 2016;8(1):38.
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Van der Doef TF, de Witte LD, Sutterland AL, Jobse E, Yaqub M, Boellaard R, de Haan L, Eriksson J, Lammertsma AA, Kahn RS, van Berckel BN. In vivo (R)[11C]PK11195 PET imaging of 18kDa translocator protein in recent onset psychosis. NPJ Schizophr. 2016;2:16031.
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2015

Boutin H, Murray K, Pradillo J, Maroy R, Smigova A, Gerhard A, Jones PA, Trigg W. [18F]GE-180: a novel TSPO radiotracer compared to [11C]PK11195 in a preclinical model of stroke. Eur J Nucl Med Mol Imaging. 2015;42(3):503-11.
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Boutin H, Pinborg L. TSPO imaging in stroke: from animal models to human subjects. Clin Transl Imaging. 2015;3(6):423-35.
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Cerami C, Crespi C, Della Rosa PA, Dodich A, Marcone A, Magnani G, Coppi E, Falini A, Cappa SF, Perani D. Brain changes within the visuo-spatial attentional network in posterior cortical atrophy. J Alzheimers Dis. 2015;43(2):385-95.
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Cerami C, Della Rosa PA, Magnani G, Santangelo R, Marcone A, Cappa SF, Perani D. Brain metabolic maps in Mild Cognitive Impairment predict heterogeneity of progression to dementia. Neuroimage Clin. 2015;7:187-94.
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Cerami C, Perani D. Imaging neuroinflammation in ischemic stroke and in the atherosclerotic vascular disease. Curr Vasc Pharmacol. 2015;13(2):218-22.
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Farde L. Spotlight: TSPO binding may also represent ‘resting’ microglia. Clin Transl Imaging. 2015;3(6):491-492.
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Farid K, Carter SF, Rodriguez-Vieitez E, Almkvist O, Andersen P, Wall A, Blennow K, Portelius E, Zetterberg H, Nordberg A. Case report of complex Amyotrophic Latera Sclerosis with cogntitive impairment and cortical amyloid deposition. J Alzheimers Dis. 2015;47(3):661-667.
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Janczar K, Su, Z, Raccagni I, Anfosso A, Kelly C, Durrenberger PF, Gerhard A, Roncaroli F. The 18-kDa mitochondrial translocator protein in gliomas: from bench to bedside. Biochem Soc Trans 2015;43:579-585.
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Jensen P, Feng L, Law I, Svarer C, Knudsen GM, Mikkelsen JD, de Nijs R, Larsen VA, Dyssegaard A, Thomsen GK, Fischer W, Guilloteau D, Pinborg LH. TSPO imaging in glioblastoma multiforme: A direct comparison between 123ICLINDE-SPECT, 18F-FET PET and gadolinium-enhanced MRI. J Nucl Med. 2015; 56(9):1386-90.
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Jensen P, Kondziella D, Thomsen G, Dyssegaard A, Svarer C, Pinborg LH. Anti-NMDAR encephalitis: Demonstration of neuroinflammation and the effect of immunotherapy. Neurology. 2015;84(8):859.
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Kumar R, Nordberg A, Darreh-Shori T. Amyloid-β peptides act as allosteric modulators of cholinergic signalling through formation of soluble BAβACs. Brain. 2016;139(Pt 1):174-92.
Read full paper via ZENODO

Lemoine L, Saint-Aubert L, Marutle A, Antoni G, Eriksson JP, Ghetti B, Okamura N, Nennesmo I, Gillberg PG, Nordberg A. Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue. Acta Neuropathol Commun. 2015;3:40.
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Maetzler W, Drey M, Jacobs AH. Sarkopenie und Frailty in der Neurologie. Nervenarzt. 2015;86(4):420-30. Read full paper via ZENODO

Nordberg A. The use of amyloid imaging in clinical praxis: a critical review. Clin Transl Imaging. 2015;3:7–11. Read full paper via ZENODO

Nordberg A, Kadir A, Andreasen N, Almkvist O, Wall A, Blennow K, Långström B, Zetterberg H. Correlations between Alzheimer disease cerebrospinal fluid biomarkers and cerebral glucoes metabolisms after 12 months of phenserine treatment. J Alzheimers Dis. 2015;47(3):691-704.
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van der Doef TF, Doorduin J, van Berckel BNM, Cervenka S. Assessing brain immune activation in psychiatric disorders: Clinical and preclinical PET imaging studies of the 18-kDa Translocator Protein. Clinical and Translational Imaging. 2015;3(6):449-460.
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Varrone A, Lammertsma AA. Editorial: Imaging of neuroinflammation: TSPO and beyond. Clinical and Translational Imaging. 2015;3(6):389-390.
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Varrone A, Nordberg A. Molecular Imaging of Neuroinflammation in Alzheimer's disease. Clinical and Translational Imaging. 2015;3(6):437-447.
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