Role of blood-brain barrier, innate immunity, and tau protein oligomerization in the pathogenesis of Alzheimer's disease

Project of the Croatian Science Foundation grant no. IP-2019-04-3584 (15 Jan 2020 - 14 Jan 2024)

Uloga krvno-moždane barijere, urođene imunosti i oligomerizacije tau proteina u patogenezi Alzheimerove bolesti

Projekt Hrvatske zaklade za znanost br. IP-2019-04-3584 (15. siječnja 2020. - 14. siječnja 2024. godine)

Hrvatska zaklada za znanost Croatian Science Foundation

Poveznica na prethodni HRZZ projekt / Link to the previous CSF project

Project collaborators / Suradnici na projektu:

Velimir Altabas, Mirjana Babić Leko, Danira Bažadona, Antonela Blažeković, Marina Boban, Mirta Boban, Srećko Branica, Lea Langer Horvat, Dražen Huić, Vesna Lukinović-Škudar, Ana Mlinarić, Martina Rinčić, Ankica Sekovanić, Ena Španić, Željka Vogrinc, Klara Zubčić

Project leader / Voditelj projekta:

Goran Šimić

Summary of the project

The amyloid cascade hypothesis explains familial cases of Alzheimer’s disease (AD) with known mutations, but is insufficient to explain sporadic, late-onset AD that accounts for over 95% of all cases. Genetic and experimental studies have implicated microglial dysfunction and blood-brain barrier (BBB) disruption as causal factors for AD. We propose an in-depth analysis of these aspects of the disease that may contribute mechanistically to the development of tau protein aggregation and neurofibrillary lesions, which show the highest correlation with clinical symptoms and progression of AD. Our aims are: 1. To examine the relationships between cognitive status of healthy controls (HC), subjects with mild cognitive impairment (MCI) and AD subjects with blood and cerebrospinal fluid (CSF) markers of innate immune activation; a battery of neuropsychological tests, MRI analysis of cortical atrophy, auditory event-related potentials will be performed, and cognition assessed by the hidden-goal test using the ALZENTIA® system we developed; 2. To determine the BBB permeability in HC, MCI, and AD subjects by measuring CSF/blood albumin ratio and levels of neurofilament light chain and S100B proteins, as well as concentrations of 24 metal, metalloids, and trace elements; 3. To evaluate neuroimmune activation in the 3 groups through assessment of CSF and blood TNF?, IL-1ß, VILIP-1, YKL-40, sTREM2, MCP1, CCL3, CCL4, and eotaxin-3, and postmortem tissue markers of neuroinflammation and M1 microglial activation (C1q, CD11b, CD68, CX3CR1, HLA-DR, IBA1, TREM2) and through immunocytochemical analysis of BBB integrity (AQP4 channels, collagen type IV) and function (LRP1, VDRLR, and RAGE receptors) in HC and AD brains as well as in Wistar rats inoculated with pathological tau oligomers; and 4. To construct a luminescent reporter for monitoring human tau oligomerization in living yeast cells, which we will use to examine the effect of proteotoxic stress and aging on tau oligomerization.

Sažetak projekta

Hipoteza amiloidne kaskade dobro objašnjava obiteljske slucajeve Alzheimerove bolesti (AD) s poznatim mutacijama, ali je nedostatna za razumijevanje nastanka sporadicne AD s kasnim pocetkom koja cini više od 95% svih slucajeva AD. Geneticka i eksperimentalna istraživanja ukazuju da bi disfunkcija mikroglije i povecana propusnost krvno-moždane barijere (BBB) mogli biti uzrocni cimbenici za nastanak AD. Zato predlažemo detaljnu analizu tih manje istraženih aspekata bolesti jer mogu doprinijeti objašnjenju agregacije tau proteina i neurofibrilarne patologije koja najbolje korelira s klinickim simptomima i napredovanjem bolesti. Naši su ciljevi: 1. ispitati odnose izmedu kognicije zdravih kontrola (HC), ispitanika s blagim spoznajnim oštecenjem (MCI) i ispitanika s AD s biološkim biljezima urodene imunosti u krvi i likvoru; osim niza neuropsiholoških testova, MR analize kortikalne atrofije i slušnih evociranih potencijala, stanje kognicije cemo procjenjivati testom skrivenog objekta pomocu vlastitog ALZENTIA® sustava; 2. odrediti propusnost BBB u HC, MCI, i AD ispitanika mjerenjem omjera albumina u likvoru i serumu te odredivanjem razine lakog lanca neurofilamenata i S100B proteina, kao i 24 metala, metaloida i elementa u tragovima; 3. procijeniti stupanj neuroimunološke aktivacije u sve 3 skupine ispitanika putem mjerenja vrijednosti TNF?, IL-1ß, VILIP-1, YKL-40, sTREM2, MCP1, CCL3, CCL4 i eotaksina-3 u krvi i likvoru te vizualizacijom neuroinflamacije i M1 mikroglije u postmortalnim uzorcima mozga (C1q, CD11b, CD68, CX3CR1, HLA-DR, Iba1, TREM2) i analize integriteta (prikaz akvaporinskih AQP4 kanala i kolagena tipa IV) i funkcije (prikaz LRP1, VDRLR i RAGE receptora) BBB u HC i AD, kao i mozgovima Wistar štakora inokuliranih patološkim tau oligomerima; i 4. Konstruirati luminescentni reporter za pracenje oligomerizacije tau proteina covjeka u živim stanicama kvasca, koje cemo koristiti za ispitivanje ucinka proteotoksicnog stresa i starenja na tau oligomerizaciju.

Project publications / Publikacije proistekle iz projekta

15. I. 2020 - 14. I. 2021

Babić Leko, M., Nikolac Perković, M., Klepac, N., Švob Štrac, D., Borovečki, F., Pivac, N., Hof, P.R., Šimić, G.
Relationship of cerebrospinal fluid Alzheimer’s disease biomarkers and COMT, DBH and MAOB single nucleotide polymorphisms
(2020) Journal of Alzheimer’s Disease 73: 135-145. (i.f. = 3,909)

Bažadona D, Fabek I, Babić Leko M, Bobić Rasonja M, Kalinić D, Bilić E, Raguž JD, Mimica N, Borovečki F, Hof PR, Šimić G.
A non-invasive hidden-goal test for spatial orientation deficit detection in subjects with suspected mild cognitive impairment (2020) Journal of Neuroscience Methods 332: 108547 (i.f. = 2,785)

Babić Leko M, Nikolac Perković M, Klepac N, Švob Štrac D, Borovečki F, Pivac N, Hof PR, Šimić G. IL-1beta, IL-6, IL-10, and TNFalpha single nucleotide polymorphisms in human influence the susceptibility to Alzheimer’s disease pathology (2020) Journal of Alzheimer’s Disease 75: 1029-1047. (i.f. = 3,909)

Šimić G. The ALZENTIA system: a sensitive non-invasive hidden goal test for early cognitive impairment screening (2020) Liječnički Vjesnik 142 (Suppl. 1): 45.

Alić I, Goh PA, Murray A, Portelius E, Gkanatsiou E, Gough G, Mok KY, Koschut, Brunmeir R, Yeap YJ, O’Brien NL, Groet J, Shao X, Havlicek S, Dunn NR, Kvartsberg H, Brinkmalm G, Hithersay R, Startin C, Hamburg S, Phillips M, Pervushin K, Turmaine M, Wallon D, Rovelet-Lecrux A, Soininen H, Volpi E, Martin JE, Foo JN, Becker DL, Rostagno A, Ghiso J, Krsnik Ž, Šimić G, Kostović I, Mitrečić D, LonDownS Consortium, Francis PT, Blennow K, Strydom A, Hardy J, Zetterberg H, Nižetić D. Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain (2020) Molecular Psychiatry 26(10): 5766-5788. (i.f. = 12,348) doi: 10.1038/s41380-020-0806-5

Zubčić K, Radovanović V, Vlainić J, Hof PR, Oršolić N, Šimić G, Jazvinšćak Jembrek M. PI3K/Akt and ERK1/2 signalling are involved in quercetin-mediated neuroprotection against copper-induced injury
(2020) Oxidative Medicine and Cellular Longevity 9834742: 1-14 (i.f. = 5,076).

Langer Horvat L, Španić E, Babić Leko M, Mladinov M, Hof Patrick R., Šimić G. Novel non-transgenic rat tauopathy model induced by injection of tau oligomers into the entorhinal cortex. FENS Forum Glasgow 11-15 July 2020. poster abstract certificate

Zubčić K, Hof PR, Šimić G, Jazvinšćak Jembrek M. The role of copper in tau-related pathology in Alzheimer’s disease (2020) Frontiers in Molecular Neuroscience 13; 572308, 1-19 (i.f. = 4,057)

Babić Leko M, Nikolac Perković M, Krbot Skorić M, Klepac N, Vogrinc Ž, Švob Štrac D, Borovečki F, Pivac N, Hof PR, Šimić G. IL-1ß single nucleotide polymorphism as potential genetic biomarker of Alzheimer's disease. Croatian congress on Alzheimer's disease with international participation – CROCAD-20v (virtual congress), 16.X.2020. Neurologia Croatica 2020; 69 (Suppl. 2): 51. (Prva nagrada za najbolji poster)

Španić E, Babić Leko M, Vogrinc D, Langer Horvat L, Šimić G. Analysis of cytokine levels in cerebrospinal fluid of mild cognitive impairment and Alzheimer's disease patient Croatian congress on Alzheimer's disease with international participation – CROCAD-20v (virtual congress), 16.X.2020. Neurologia Croatica 2020; 69 (Suppl. 2): 50.

Langer Horvat L, Španić E, Babić Leko M, Šimić G. Novel non-transgenic rat tauopathy model induced by injection of tau oligomers into the entorhinal cortex Croatian congress on Alzheimer's disease with international participation – CROCAD-20v (virtual congress), 16.X.2020. Neurologia Croatica 2020; 69 (Suppl. 2): 48. (Prva nagrada za najbolji poster)

Nikolac Perković M, Čuljak M, Uzun S, Švob Štrac D, Nedić Erjavec G, Babić Leko M, Šimić G, Tudor L, Konjevod M, Kozumplik O, Mimica N, Pivac N.
Citokini u Alzheimerovoj bolesti. Croatian congress on Alzheimer's disease with international participation – CROCAD-20v (virtual congress), 16.X.2020. Neurologia Croatica 2020; 69 (Suppl. 2): 19.

Šimić G. Personalized treatment of Alzheimer's disease based on estimated activators of Aß deposition. Croatian congress on Alzheimer's disease with international participation – CROCAD-20v (virtual congress), 16.X.2020. Neurologia Croatica 2020; 69 (Suppl. 2): 23.

Čuljak M, Nikolac Perković M, Uzun S, Švob Štrac D, Nedić Erjavec G, Babić Leko M, Šimić G, Tudor L, Konjevod M, Kozumplik O, Mimica N, Pivac N. The association between TNFalpha, IL-1alpha and IL-10 with Alzheimer’s disease (2020) Current Alzheimer’s Research 17(11): 972-984. doi: 10.2174/1567205017666201130092427 (i.f. = 3,047)

Lemoine L, Ledreux A, Mufson EJ, Perez SE, Šimić G, Doran E, Lott I, Carroll S, Bharani K, Thomas S, Gilmore A, Hamlett ED, Nordberg A, Granholm A-C (2020) Regional binding of tau and amyloid PET tracers in Down syndrome autopsy brain tissue. Molecular Neurodegeneration 15: 68 (i.f. = 9,599)

Zubčić K, Šimić G, Jazvinšćak Jembrek M. p53-mediated neuroprotective effects of natural compounds in oxidative stress conditions. In: p53 – structure, function and role in disease (ed. Stevens, M.) Nova Science Publishers, New York, 2020, pp. 127-181.

Šimić G, Vukić V, Kopić J, Krsnik Ž, Hof PR. Molecules, mechanisms, and disorders of self-domestication: keys for understanding emotional and social communication from an evolutionary perspective (2021) Biomolecules 11 (1), 2 (i.f. = 4,082)

15. I. 2021 - 14. VII. 2022

Babić Leko, M., Hof P.R., Šimić, G. (2021) Alterations and interactions of subcortical modulatory systems in Alzheimer’s disease (2021) Progress in Brain Research 261: 379-421 (i.f. = 2,453)

Babić Leko, M., Jurasović, J., Nikolac Perković, M., Španić, E., Sekovanić, A., Orct, T., Lukinović Škudar, V., Bačić Baronica, K., Kiđemet-Piskač, S., Vogrinc, Ž., Pivac, N., Borovečki, F., Hof, P.R., Šimić, G. (2021) The association of essential metals with APOE genotype in Alzheimer’s disease. Journal of Alzheimer's disease 82(2): 661-672.
doi: 10.3233/JAD-210158 (i.f. = 4,472)

Šimić, G., Tkalčić, M., Vukić, V., Mulc, D., Španić, E., Šagud, M., Olucha-Bordonau, F.E., Vukšić, M., Hof, P.R. (2021) Understanding emotions: origins and roles of the amygdala. Biomolecules 11: 823 (i.f. = 4,879)

Švob Štrac, D., Konjevod, M., Šagud, M., Nikolac Perković, M., Nedić Erjaveć, G., Vuic, B., Šimić, G., Vukić, V., Mimica, N., Pivac, N. (2021) Personalizing the care and treatment of Alzheimer's disease: an overview. Pharmacogenomics and Personalized Medicine 14: 631-653 (i.f. = 3,912)

Žigman, T., Petkovic-Ramadža, D., Šimić, G., Barić, I. (2021) Inborn errors of metabolism associated with autism spectrum disorders: approaches to intervention. Frontiers in Neuroscience 15, 673600 (i.f. = 4,677)

Babić Leko M, Jurasović J, Nikolac Perković M, Španić E, Sekovanić A, Orct T, Lukinović Škudar V, Bačić Baronica, Kiđemet-Piskač S, Vogrinc Ž, Pivac N, Borovečki F, Hof, PR, Šimić G. (2021) APOE genotype and essential metals in Alzheimer's disease. 1st Congress of the Croatian Alzheimer Alliance with international participation, May 19-21, 2021
Neurologia Croatica 2021; 70 (Suppl. 1): 39-40.

Pivac N, Nikolac Perković M, Babić Leko M, Borovečki F, Švob Štrac D, Nedić Erjavec G, Mimica N, Šimić G. (2021) Genske varijante moždanog neurotrofnog čimbenika moduliraju biomarkere iz cerebrospinalne tekućine u ispitanika s Alzheimerovom bolesti. 1. Kongres Hrvatske Alzheimer alijanse s medunarodnim sudjelovanjem, 19-21. svibnja 2021.
Neurologia Croatica 2021; 70 (Suppl. 1): 47.

Babić Leko M, Nikolac Perković M, Nedić Erjavec G, Klepac N, Švob Štrac D, Borovečki F, Pivac N, Hof PR, Šimić G. (2021) Povezanost polimorfizma jednog nukleotida u genima za MAOB i APOE u Alzheimerovoj bolesti. 1. Kongres Hrvatske Alzheimer alijanse s medunarodnim sudjelovanjem, 19-21. svibnja 2021.
Neurologia Croatica 2021; 70 (Suppl. 1): 111.

Jurković Ana (2021) Povezanost samodomestikacije čovjeka i poremećaja iz autističnog spektra. Diplomski rad. Medicinski fakultet Sveučilišta u Zagrebu.

Zujić Branimira (2021) Utjecaj bioaktivnih lipida na upalne procese, urođenu imunost i emocionalnu regulaciju. Diplomski rad. Medicinski fakultet Sveučilišta u Zagrebu.

Horvat Velić Emina (2021) Analysis of tau protein propagation in the rat brain as a model of Alzheimer's disease. Diploma Thesis. Faculty of Science, University of Zagreb.

Babić Leko M, Nikolac Perković M, Nedić Erjavec G, Klepac N, Švob Štrac D, Borovečki F, Pivac N, Hof PR, Šimić G (2021) Association of the MAOB rs1799836 single nucleotide polymorphism and APOE epsilon4 allele in Alzheimer's disease. Current Alzheimer's Research 18 (7): 585-594. (i.f. = 3,498) 1160933

Šimić, G., Krsnik, Ž., Knezović, V., Kelović, Z., Mathiasen M. L., Junaković, A., Radoš, M., Mulc, D., Španić, E., Quattrocolo, G., Hall, V.H., Zaborszky, L., Vukšić, M., Bordonau, F. O., Kostović, I., Witter, M. P., Hof, P.R. Prenatal development of the human entorhinal cortex (2022) The Journal of Comparative Neurology 530(15): 2711-2748. doi: 10.1002/cne.25344. 1195742 (i.f. = 3,215)

Sitaš, B., Bobić-Rasonja, M., Mrak, G., Trnski, S., Krbot Skorić, M., Orešković, D., Knezović, V., Petelin Gadže, Ž., Petanjek, Z., Šimić, G., Kolenc, D., Jovanov Milošević, N. (2022) Reorganization of the brain extracellular matrix in hippocampal sclerosis. International Journal of Molecular Sciences 23(15): 8197. (i.f. = 6.208)

15. VII. 2022. - 14. VI. 2024.

Španić, E., Langer Horvat, L., Ilić, K., Hof, P.R., Šimić, G. (2022) NLRP1 inflammasome activation in the hippocampal formation in Alzheimer's disease: correlation with neuropathological changes and unbiasedly estimated neuronal loss. Cells 11(14): 2223. 1206137 (i.f. = 7,666)

Golubić, A. T., Huić, D., Šimić, G. Biomarkers – emerging concepts in Alzheimer's disease. Alzheimer's disease: update 2022. Manual of the University of Zagreb School of Medicine, Medicinska naklada, Zagreb, 2022, pp. 8-12. 1215049

Štampar, E. “Expression of LRP1 receptor in the hippocampal formation in healthy and subjects with Alzheimer's disease”, 2022, Diploma Thesis, 1225494

Španić, E., Šimić, G. Fiziološke promjene mozga s dobi i vulnerabilnost za nastanak psihičkih poremećaja (poglavlje 3). U: Psihijatrija starije dobi (ur. Mimica, N., Kušan Jukić, M. i suradnici), Sveučilišni udžbenik, Medicinska naklada Zagreb, pp. 12-26. 1221852

Klara Zubčić, mag. biol. mol., “Influence of proteotoxic stress on aggregation and toxicity of a human tau protein expressed in the yeast Saccharomyces cerevisiae”, PhD thesis defended on 12.XII.2022. 1249249

Lea Langer Horvat, mag. biol. mol., “Development and characterization of a non-transgenic rat model of tauopathy induced by injection of tau protein into the entorhinal cortex”, PhD thesis defended on 14.XII.2022. 1249254

Babić Marija, Banović Maria, Berečić Ivana (Goran Šimić - mentor, University of Zagreb School of Medicine), Total tau protein, light chain of neurofilaments, and S100B protein in the cerebrospinal fluid of spinal atrophy patients treated with nusinersen („Ukupni tau protein, laki lanac neurofilamenta i S100B protein u likvoru bolesnika sa spinalnom mišićnom atrofijom liječenih nusinersenom“), University of Zagreb School of Medicine Dean's Award for the best students work 2022. (Nagrada dekana Medicinskog fakulteta Sveučilišta u Zagrebu za najbolji studentski rad znanstveni 2022. godine) 1251557

Ena Španić Popovački, mag. biol. exp., “Association of inflammation mediators with microglial and inflammasome activation and CSF biomarkers of Alzheimer's disease”, PhD thesis defended on 12.I.2023. 1250302

Babić Leko, M., Nikolac Perković, M., Španić, E., Švob Štrac, D., Pleić, N., Vogrinc, Ž., Gunjača, I., Bežovan, D., Nedić Erjavec, G., Klepac, N., Borovečki, F., Zemunik, T., Pivac, N., Hof, P.R., Šimić, G.
Serotonin receptor gene polymorphisms are associated with cerebrospinal fluid, genetic, and neuropsychological biomarkers of Alzheimer’s disease. Biomedicines 2022, 10(12), 3118. (i.f. = 4,757) 1237806

Šimić G., Vukić, V., Babić, M., Banović, M., Berečić, I.,Španić, E., Zubčić, K., Golubić, A.T., Barišić Kutija, M., Merkler Šorgić, A., Vogrinc, Ž., Lehman, I., Hof, P.R., Sertić, J., Barišić, N.
Total tau in cerebrospinal fluid detects treatment responders among spinal muscular atrophy types 1-3 patients treated with nusinersen.
CNS Neuroscience & Therapeutics 2022; doi: 10.1111/cns.14051 (i.f. = 7,035) 1248439

Babić Leko, M., Mihelčić, M., Jurasović, J., Nikolac Perković, M., Španić, E., Sekovanić, A., Orct, T., Zubčić, K., Langer Horvat, L., Pleić, N., Kiđemet-Piskač, S., Vogrinc, Ž., Pivac, N., Diana, A., Borovečki, F., Hof, P.R., Šimić, G. Heavy metals and essential metals are associated with cerebrospinal fluid biomarkers of Alzheimer’s disease. International Journal of Molecular Sciences 2022; 24(1), 467. (i.f. = 6,208) 1249190

Langer Horvat, L., Španić Popovački, E., Babić Leko, M., Zubčić, K., Horvat, L., Mustapić, M., Hof, P. R., Šimić, G. Anterograde and retrograde propagation of inoculated human tau fibrils and human tau oligomers in a non-transgenic rat tauopathy model. (2023) Biomedicines 11(4), 1004. (i.f. = 4,757) 1263284

Babić Leko, M., Langer Horvat, L., Španić Popovački, E., Zubčić, K., Hof, P. R., Šimić, G. Metals in Alzheimer’s disease (2023) Biomedicines 11(4). 1161 (i.f. = 4,757) 1266481

Zubčić, K., Franić, D., Pravica, M., Hof, P. R., Šimić, G., Boban, M. Effects of heterologous human tau protein expression in yeast models of proteotoxic stress response.
June 21, 2023 CNS Neuroscience & Therapeutics doi: 10.1111/cns.14304. (i.f. = 7,035) 1280388

Španić Popovački, E., Babić Leko, M., Langer Horvat, L., Brgić, K., Vogrinc, Ž., Boban, M., Klepac, N., Borovečki, F., Šimić, G. Soluble TREM2 concentrations in the cerebrospinal fluid correlate with the severity of neurofibrillary degeneration, cognitive impairment, and inflammasome activation in Alzheimer’s disease. Neurology International 2023; 15(3): 842-856. (i.f. =3,0) 798337

Babić, M., Banović, M., Berečić, I., Banić, T., Babić Leko, M., Ulamec, M., Junaković, A., Kopić, J., Sertić, J., Barišić, N., Šimić, G. Molecular biomarkers for the diagnosis, prognosis, and pharmacodynamics of spinal muscular atrophy. Journal of Clinical Medicine 2023; 12(15): 5060. (i.f. = 4,964) 798338

Mulc, D., Smilović, D., Krsnik, Ž., Junakovic-Munjas, A., Kopić, J., Kostović, I., Šimić, G., Vukšić, M. Fetal development of the human amygdala (2024) The Journal of Comparative Neurology 532(1): e25580. (i.f. = 3,028)

Vogrinc, D. Usporedba izraženosti NLRP1 inflamasoma u čeonom režnju zdravih odraslih osoba i bolesnika sa shizofrenijom (2023) Medicinski fakultet Sveučilišta u Zagrebu, Diplomski rad.

Španić Popovački, E., Vogrinc, D., Fuller H. R., Langer Horvat, L., Mayer, D., Kopić, J., Babić Leko M., Pravica, M., Krsnik, Ž., Marčinko, D., Šagud, M., Hof, P.R., Mladinov, M., Šimić, G.
Increased NLRP1 mRNA and protein expression suggests inflammasome activation in the dorsolateral prefrontal and medial orbitofrontal cortex in schizophrenia
Biomolecules 2024; 14(3): 302. (i.f. = 5,5)

Dina Franić: „Selektivna razgradnja pogrešno smotanih proteina u stanicama kvasca Saccharomyces cerevisiae u mirovanju“ / "Selective degradation of misfolded proteins in quiescent Saccharomyces cerevisiae cells" (supervisor: Mirta Boban), Ph.D. thesis defended on April 15, 2024.

Verma R, Jayakumar J, Folkerth R, Manger PR, Bota M, Majumder M, Pandurangan K, Savoia S, Karthik S, Kumarasami R, Joseph J, Rohini G, Vasudevan S, Srinivasan C, Lata S, Kumar EH, Rangasami R, Kumutha J, Suresh, Šimić G, Mitra PP, Sivaprakasam M. Histological characterization and development of mesial surface sulci in the human brain at 13-15 weeks through hish-resolution histology
Journal of Comparative Neurology 2024; 532(4): e25612. (i.f. = 2,5)

Presentations related to the project / Predavanja i prezentacije projekta

15. I. 2020 - 14. I. 2021

Poremećaji neotenije i samodomestikacije kao mogući mehanizmi nastanka shizofrenije i autizma // Pozvano predavanje Zavoda za fiziologiju i imunologiju Medicinskog fakulteta Sveučilišta u Zagrebu, 14.I.2020. 1047141

Patogeneza autizma // Pozvano predavanje Hrvatskog pedijatrijskog društva Hrvatskog liječničkog zbora, Zagreb, 27.II.2020. 1063596
ppt

Šimić, G. The ALZENTIA system: a sensitive non-invasive hidden goal test for early cognitive impairment screening. Better Future of Healthy Ageing conference.
Zagreb, Škola narodnog zdravlja „Andrija Štampar“, Zagreb, 3.VI.2020. 1071257

Večernji list - PANORAMA 14. srpnja 2020. - osvrt na znanstveni članak u Molecular Psychiatry

Total Croatian News 27th July 2020

15. I. 2021 - 14. VII. 2022

Šimić, G. Mozak i emocije, pozvano predavanje. Stručni skup za stručne suradnike pedagoge u srednjim školama Grada Zagreba i stručne suradnike u uceničkim domovima RH. Županijsko stručno vijeće stručnih suradnika pedagoga srednjih škola Grada Zagreba i Županijsko stručno vijeće stručnih suradnika u učeničkim domovima RH. Zagreb, Škola za medicinske sestre Mlinarska, 19.III.2021. 1119547

Šimić, G. Biomarkerska specificnost demencija frontotemporalnog spektra i Alzheimerove bolesti. Poslijediplomski tečaj „Alzheimerova bolest i frontotemporalna demencija u kliničkoj praksi“
Zagreb, 17.IX.2021. ppt

Šimić, G. Povećava li opća anestezija rizik za Alzheimerovu bolest? Drugi hrvatski kongres o neurodegenerativnim bolestima s medunarodnim sudjelovanjem
Zagreb, 28.X.2021. ppt

Šimić, G. Važnost čitanja za razvoj emocionalnih kompetencija. Čitatelj i čitanje u digitalno doba. Međunarodni interdisciplinarni znanstveni skup.
Hrvatsko katoličko sveučilište, Zagreb, 11.XI.2021.

Šimić, G. Kavli lecture: Role of subputaminal nucleus in language: enigma of primary progressive aphasia solved? Kavli Institute for Systems Neuroscience at NTNU, lecture invited by prof. Menno Witter,
Trondheim, 12.XI.2021. ppt

intervju Nacional 22.III.2022.

Šimić, G. Emerging biomarker concepts in the Alzheimer's disease. Symposium of the continuing medical education “Alzheimer’s disease: update 2022”
"Klovićevi dvori" Gallery, Zagreb, 16.IX.2022. 1215368

Šimić, G., Babić Leko, M., Mihelčić, M. Dynamics of blood and cerebrospinal fluid biomarkers of Alzheimer's disease. Symposium “Marin Bulat: The influence of the movement of interstitial and cerebrospinal fluid on the distribution of drugs, metabolites and biomarkers within the craniospinal space". 10th Croatian Congress of Pharmacology and 1st Croatian Congress of Clinical Pharmacology. (2022) Pharmaca 52 (Suppl. 2): 136. Opatija, 25.IX.2022. 1222249

Tudor, L., Nikolac Perković, M., Babić Leko, M., Videtić Paska, A., Kouter, K., Miloš, T., Nedic Erjavec, G., Vuić B., Konjevod, M., Šimić, G., Borovečki, F., Pivac, N. Epigenetic, genetic and expression analysis of brain-derived neurotrophic factor in Alzheimer's disease. 10th Croatian Congress of Pharmacology and 1st Croatian Congress of Clinical Pharmacology. (2022) Pharmaca 52 (Suppl. 2): 75. 1229004

Zubčić, K., Franić, D., Pravica, M., Šimić, G., Boban M. A yeast model for studying human tau protein. International Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB-22, Book of Abstracts, P100, p. 161. Brela 28.IX. – 1.X.2022. 1229002

Šimić, G. Misconceptions and potential improvements of cerebrospinal fluid and blood diagnostics of neurological diseases. Professional meeting of the University Clinical Hospital "Zagreb" Neurology Clinic, Zagreb, 13.X.2022. 1225511

Babić Leko, M., Nikolac Perković, M., Švob Štrac, D., Pleić, N., Gunjača, I., Klepac, N., Borovečki, F., Pivac, N., Zemunik, T., Hof, P. R., Šimić, G.
The association of polymorphisms within serotonin receptor genes with cerebrospinal fluid, genetic, and neuropsychological biomarkers of Alzheimer's disease.
CROCAD-22 Croatian congress on Alzheimer's disease with international participation. (2022) Neurologia Croatica 71 (Suppl. 3): 61.
Supetar, Brač, 5-8.X.2022. 1222086

Langer Horvat, L., Šimić, G. Development of a non-transgenic rat model of tauopathy induced by injection of tau protein into the medial entorhinal cortex.
CROCAD-22 Croatian congress on Alzheimer's disease with international participation. (2022) Neurologia Croatica 71 (Suppl. 3): 60. (Prva nagrada za najbolji poster)
Supetar, Brač, 5-8.X.2022. 1222085

Šimić, G. Consciousness changes in persons with Alzheimer's disease. CROCAD-22 Croatian congress on Alzheimer's disease with international participation.
(2022) Neurologia Croatica 71 (Suppl. 3): 25. Supetar, Brač, 5-8.X.2022. 1222084

Šimić, G. Redefining the role of microglial cells in the pathogenesis of psychiatric and neurodegenerative diseases. CROCAD-22 Croatian congress on Alzheimer's disease with international participation. (2022) Neurologia Croatica 71 (Suppl. 3): 20. Supetar, Brač, 5-8.X.2022. 1222083

Šimić, G. Development of consciousness. (2022) Paediatria Croatica (Suppl. 1): 12-13. 3. Croatian children's health congress with international participation.
Poreč, 28-30.X.2022. 1225504

Španić Popovački, E., Šimić, G. Alzheimer's disease biomarkers. Alzheimer's disease Academy with international participation. The Ethnological museum Zagreb.
Zagreb, 3-4.II.2023. 1251843

Šimić, G., Vukšić, M. Svijest i pamćenje. HAZU Simpozij "Neurobiologija, ontogeneza i evolucija svijesti i samosvijesti u čovjeka", Zagreb, 16.III.2023. 1261936

Šimić, G. Mozak i svijest. Predavanje za pedagoge grada Zagreba u okviru 22. Tjedna mozga u Hrvatskoj. Zdravstveno veleučilište, Mlinarska 38. 17.III.2023. 1261955

Španić Popovacki, E., Babić Leko, M., Brgić, K., Vogrinc, Ž., Boban, M., Klepac, N., Borovecki, F., Šimić, G. Cytokine and chemokine levels in the cerebrospinal fluid and plasma samples of mild cognitive impairment and Alzheimer's disease subjects. 2nd Congress of the Croatian Alzheimer Alliance (2023) Neurologia Croatica 72 (Suppl. 1): 75. Varaždin, 29.III.-1.IV.2023. 1264723 (Treća nagrada za najbolji poster)

Langer Horvat, L., Šimić, G. Novel non-transgenic tauopathy model induced by inoculation of human tau fibrils and tau oligomers into the rat entorhinal cortex. 2nd Congress of the Croatian Alzheimer Alliance
(2023) Neurologia Croatica 72 (Suppl. 1): 73-74. Varaždin, 29.III.-1.IV.2023. 1264721

Pivac, N., Nikolac Perković, M., Videtić Paska, A., Nedić Erjavec, G., Uzun, S., Kozumplik, O., Borovečki, F., Filipčić, I., Mimica, N., Babić Leko, M., Šimić, G., Švob Štrac, D. The association between the catechol-O-methyltransferase (COMT) genotpes with cognition in dementia. 2nd Congress of the Croatian Alzheimer Alliance (2023) Neurologia Croatica 72 (Suppl. 1): 30. Varaždin, 29.III.-1.IV.2023. 1264718

Šimić, G. Development of antisense oligonucleotides for therapy of neurodegenerative diseases. 2nd Congress of the Croatian Alzheimer Alliance (2023) Neurologia Croatica 72 (Suppl. 1): 22. Varaždin, 29.III.-1.IV.2023. 1264175 youtube

Šimić, G. Od unutarnjih i vanjskih čimbenika učenja do motivacije. Državni skup Agencije za odgoj i obrazovanje "Primjena novih jezikoslovnih spoznaja u ostvarivanju odgojno-obrazovnih ishoda jezika i komunikacije", Zagreb, Prirodoslovna škola Vladimira Preloga, 13.IV.2023. 1266488

Šimić, G. Biomarkeri za Alzheimerovu bolest iz cerebrospinalne tekućine i plazme. 8. hrvatski kongres "Dileme u neurologiji" 10-13.V.2023. Bol, Brač ppt 1274207

Šimić, G. Transgeneracijska trauma - ekperimentalni modeli i epigenetičke promjene. Poslijediplomski tečaj "Transgeneracijska trauma" 26.V.2023. Zagreb ppt 1277476

Berečić, I., Babić, M., Banović, M., Španić, E., Vukić, V., Vogrinc, Ž., Sertić, J., Barišić, N., Šimić, G. S100 calcium-binding protein B in cerebrospinal fluid of spinal atrophy patients patients treated with nusinersen. 12. Student Congress of Neuroscience – NeuRi 2023 NeuRi Book of Abstracts: 42-43. Rijeka – Rab 21-23.IV.2023. 1268422

Banović, M., Berečić, I., Babić, M., Španić, E., Vukić, V., Vogrinc, Ž., Sertić, J., Barišić, N., Šimić, G. Levels of neurofilament light chain protein in cerebrospinal fluid of spinal muscular atrophy patients treated with nusinersen. 12. Student Congress of Neuroscience – NeuRi 2023 NeuRi Book of Abstracts: 41. Rijeka – Rab 21-23.IV.2023. 1268423

Babić, M., Banović, M., Berečić, I., Španić, E.,Vukić, V., Vogrinc, Ž., Sertić, J., Barišić, N., Šimić, G. Change of total tau protein in cerebrospinal fluid of patients with spinal muscular atrophy after nusinersen treatment. 12. Student Congress of Neuroscience – NeuRi 2023 NeuRi Book of Abstracts: 39-40. (The third place prize for the best poster) Rijeka – Rab 21-23.IV.2023. 1268424

Langer Horvat, L., Španić Popovački, E., Šimić, G. Inoculation of human tau fibrils and tau oligomers into the medial entorhinal cortex produces a novel non-transgenic rat tauopathy model
(2023) Book of Abstracts of The Second Annual Meeting of the ProteoCure COST Action, p. 77, Zagreb 12-15.VI.2023. 1281675

Golubić, A. T., Huić, D., Šimić, G. Biomarkers in the diagnosis of Alzheimer's disease and Lewy body dementia. Postgraduate course “Alzheimer's and Parkinson’s disease, and Lewy body dementia: update 2023”, Medicinska naklada, Zagreb, 2023, pp. 8-13. Zagreb 15.IX.2023. 799775

Langer Horvat, L., Šimić, G. Phosphorylated tau protein expression following inoculation of human tau oligomers and synthetic tau fibrils into the rat medial entorhinal cortex. 9th Croatian Neuroscience Congress, Osijek, 17-19.XI.2023. 810825

Šimić, G. Can AI be conscious? Alliance4Life Early Stage Researchers' Retreat “AI in Science and Research Visibility“ Zagreb, 17.I.2024. 836044 ppt

Šimić G. Evolucija usamljenosti (i društvenosti) Evolution of loneliness (and sociability). Simpozij "Usamljenost i depresija" / Symposium “Loneliness and depression“, Klinički bolnički centar Zagreb / University Hospital Centre Zagreb, May 24, 2024. 835579 ppt

Španić Popovački, E., Vogrinc, D., Fuller H. R., Langer Horvat, L., Mayer, D., Kopić, J., Pintarić, K., Babić Leko M., Pravica, M., Krsnik, Ž., Marčinko, D., Šagud, M., Hof, P.R., Mladinov, M., Šimić, G.
NLRP1 inflammasome activation in schizophrenia. FENS Forum 2024, Vienna, June 25-29, 2024 835903 ppt

Please send questions related to the project to / Molimo šaljite pitanja vezana uz projekt na

goransimic@hotmail.com

page last updated on 28th June 2024 / stranica zadnji put obnovljena 28. lipnja 2024.

Hvala na posjeti - Thank you for coming!