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Neurobiology of Alzheimer's disease: risk markers, prognosis and therapeutic response

Abstract

Since 1997, with the support of two Projetos Temáticos granted by FAPESP, our laboratory has been performing translational research applied to the analysis of the membrane phospholipids abnormalities, with a special focus on its influence in brain homeostasis and its downstream impact in neuropsychiatric diseases. In this new project, multiple biological mechanisms related to the pathophysiology of Alzheimer disease (AD) will be evaluated, in a search for clinical correlates of the higher risk of dementia in elderly patients with cognitive and mood disorders. This multidisciplinary project is divided in two modules: in module 1 (Clinical, Laboratorial and Neuroimaging studies), biological markers that influence risk, clinical course and therapeutic response will be determined after investigating DNA polymorphisms, biomarkers in the cerebro-spinal fluid and peripheral blood, as well as structural and functional brain imaging using MRS and PET. Our main goal is to establish tools for an early diagnosis of AD and to evaluate the effectiveness of pharmacological and no pharmacological interventions in reducing of cognitive impairment, with the final aim of preventing the establishment of dementia. In module 2 (Neurochemistry and Molecular Biology), in vitro (primary neuronal cultures) and in vivo (transgenic mice that accumulate beta-amyloid, Aβ, within the brain) experimental models will be used to study the inter-related molecular mechanisms involved in the pathogenesis of AD. Aβ ¬toxicity will be investigated with a focus on its impact over neurogenesis, enzymatic activity and gene expression. Due to its neurotrophic and neuroprotective activities, the capability of lithium to modulate these processes will be investigated in pre-clinical models, amalgamating all experimental and clinical aspects of this project. (AU)

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Scientific publications (46)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROCHA, NICOLE KEMBERLY R.; THEMOTEO, RAFAEL; BRENTANI, HELENA; FORLENZA, ORESTES V.; DE PAULA, VANESSA DE JESUS RODRIGUES. Neuronal-Glial Interaction in a Triple-Transgenic Mouse Model of Alzheimer's Disease: Gene Ontology and Lithium Pathways. FRONTIERS IN NEUROSCIENCE, v. 14, DEC 1 2020. Web of Science Citations: 0.
DE-PAULA, VANESSA J.; DOS SANTOS, CARLA CRISTINE C.; LUQUE, MARIA CAROLINA A.; ALI, TACCYANA M.; KALIL, JORGE E.; FORLENZA, ORESTES V.; CUNHA-NETO, EDECIO. Acute and chronic lithium treatment increases Wnt/beta-catenin transcripts in cortical and hippocampal tissue at therapeutic concentrations in mice. METABOLIC BRAIN DISEASE, v. 36, n. 1 NOV 2020. Web of Science Citations: 0.
IBARRA, ROMEL; RADANOVIC, MARCIA; PAIS, V, MARCOS; TALIB, LEDA L.; FORLENZA, V, ORESTES. AD-Related CSF Biomarkers Across Distinct Levels of Cognitive Impairment: Correlations With Global Cognitive State. JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY, AUG 2020. Web of Science Citations: 0.
LOUREIRO, JULIA C.; PAIS, MARCOS V.; STELLA, FLORINDO; RADANOVIC, MARCIA; TEIXEIRA, ANTONIO LUCIO; FORLENZA, ORESTES V.; DE SOUZA, LEONARDO CRUZ. Passive antiamyloid immunotherapy for Alzheimer's disease. CURRENT OPINION IN PSYCHIATRY, v. 33, n. 3, p. 284-291, MAY 2020. Web of Science Citations: 1.
BRAM, JESSYKA MARIA DE FRANCA; TALIB, LEDA LEME; JOAQUIM, HELENA PASSARELLI GIROUD; SARNO, TAMIRES ALVES; GATTAZ, WAGNER FARID; FORLENZA, ORESTES VICENTE. Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 269, n. 8, p. 963-972, DEC 2019. Web of Science Citations: 2.
FORLENZA, ORESTES V.; RADANOVIC, MARCIA; TALIB, LEDA L.; GATTAZ, WAGNER F. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. BRITISH JOURNAL OF PSYCHIATRY, v. 215, n. 5, p. 668-674, NOV 2019. Web of Science Citations: 3.
RADANOVIC, MARCIA; OSHIRO, CARLOS A.; FREITAS, THIAGO Q.; TALIB, LEDA L.; FORLENZA, ORESTES V. Correlation between CSF biomarkers of Alzheimer's disease and global cognition in a psychogeriatric clinic cohort. Revista Brasileira de Psiquiatria, v. 41, n. 6, p. 479-484, NOV-DEC 2019. Web of Science Citations: 1.
DE OLIVEIRA, ALEXANDRA MARTINI; RADANOVIC, MARCIA; HOMEM DE MELLO, PATRICIA COTTING; BUCHAIN, PATRICIA CARDOSO; VIZZOTTO, ADRIANA DIAS; HARDER, JANAINA; STELLA, FLORINDO; PIERSOL, CATHERINE VERRIER; GITLIN, LAURA N.; FORLENZA, ORESTES VICENTE. An intervention to reduce neuropsychiatric symptoms and caregiver burden in dementia: Preliminary results from a randomized trial of the tailored activity program-outpatient version. INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, v. 34, n. 9, SI, p. 1301-1307, SEP 2019. Web of Science Citations: 2.
VACAS, SARA M.; STELLA, FLORINDO; LOUREIRO, JULIA C.; DO COUTO, FREDERICO SIMOES; OLIVEIRA-MAIA, ALBINO J.; FORLENZA, ORESTES V. Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: A systematic review and meta-analysis. INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, v. 34, n. 9, SI, p. 1336-1344, SEP 2019. Web of Science Citations: 1.
MÁRCIA RADANOVIC; CARLOS A. OSHIRO; THIAGO Q. FREITAS; LEDA L. TALIB; ORESTES V. FORLENZA. Correlation between CSF biomarkers of Alzheimer’s disease and global cognition in a psychogeriatric clinic cohort. Revista Brasileira de Psiquiatria, n. ahead, p. -, 2019.
MÁRCIA RADANOVIC; CARLOS A. OSHIRO; THIAGO Q. FREITAS; LEDA L. TALIB; ORESTES V. FORLENZA. Correlation between CSF biomarkers of Alzheimer’s disease and global cognition in a psychogeriatric clinic cohort. Revista Brasileira de Psiquiatria, v. 41, n. 6, p. 479-484, Dez. 2019.
DE-PAULA, VANESSA DE J. R.; FORLENZA, ANDREA S.; FORLENZA, ORESTES V. Relevance of gutmicrobiota in cognition, behaviour and Alzheimer's disease. PHARMACOLOGICAL RESEARCH, v. 136, p. 29-34, OCT 2018. Web of Science Citations: 10.
RADANOVIC, MARCIA; FACCO, GIULIANA; FORLENZA, ORESTES V. Sensitivity and specificity of a briefer version of the Cambridge Cognitive Examination (CAMCog-Short) in the detection of cognitive decline in the elderly: An exploratory study. INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, v. 33, n. 5, p. 769-778, MAY 2018. Web of Science Citations: 0.
CARDILLO, GIANCARLO DE MATTOS; RODRIGUES DE-PAULA, VANESSA DE JESUS; IKENAGA, ELIZA HIROMI; COSTA, LUCIANA RODRIGUES; CATANOZI, SERGIO; SCHAEFFER, EVELIN LISETE; GATTAZ, WAGNER FARID; KERR, DANIEL SHIKANAI; FORLENZA, ORESTES VICENTE. Chronic Lithium Treatment Increases Telomere Length in Parietal Cortex and Hippocampus of Triple-Transgenic Alzheimer's Disease Mice. JOURNAL OF ALZHEIMER'S DISEASE, v. 63, n. 1, p. 93-101, 2018. Web of Science Citations: 3.
STELLA, FLORINDO; LOUREIRO, JULIA C.; PAIS, MARCOS V.; CANINEU, PAULO R.; FORLENZA, ORESTES V. Safety Limits of Antidepressant Use Plus Combinations: Focus on Cardiovascular Function. CURRENT DRUG METABOLISM, v. 19, n. 8, p. 641-652, 2018. Web of Science Citations: 2.
MIRANDEZ, ROBERTA M.; APRAHAMIAN, IVAN; TALIB, LEDA L.; FORLENZA, ORESTES V.; RADANOVIC, MARCIA. Multiple category verbal fluency in mild cognitive impairment and correlation with CSF biomarkers for Alzheimer's disease. INTERNATIONAL PSYCHOGERIATRICS, v. 29, n. 6, p. 949-958, JUN 2017. Web of Science Citations: 5.
FORLENZA, ORESTES V.; LOUREIRO, JULIA CUNHA; PAIS, MARCOS VASCONCELOS; STELLA, FLORINDO. Recent advances in the management of neuropsychiatric symptoms in dementia. CURRENT OPINION IN PSYCHIATRY, v. 30, n. 2, p. 151-158, MAR 2017. Web of Science Citations: 9.
MÁRCIA RADANOVIC; FLORINDO STELLA; LIS GOMES SILVA; LEDA L. TALIB; ORESTES V. FORLENZA. Increased CSF levels of total Tau in patients with subcortical cerebrovascular pathology and cognitive impairment. Dement. Neuropsychol., v. 11, n. 4, p. -, Dez. 2017.
SARNO, TAMIRES ALVES; TALIB, LEDA LEME; GIROUD JOAQUIM, HELENA PASSARELLI; DE FRANCA BRAM, JESSYKA MARIA; GATTAZ, WAGNER FARID; FORLENZA, ORESTES VICENTE. Protein Expression of BACE1 is Downregulated by Donepezil in Alzheimer's Disease Platelets. JOURNAL OF ALZHEIMER'S DISEASE, v. 55, n. 4, p. 1445-1451, 2017. Web of Science Citations: 2.
SCHAEFFER, EVELIN L.; CATANOZI, SERGIO; WEST, MARK J.; GATTAZ, WAGNER F. Stereological investigation of the CA1 pyramidal cell layer in untreated and lithium-treated 3xTg-AD and wild-type mice. ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, v. 209, p. 51-60, 2017. Web of Science Citations: 6.
DE-PAULA, VANESSA J.; GATTAZ, WAGNER F.; FORLENZA, ORESTES V. Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at subtherapeutic concentrations. BIPOLAR DISORDERS, v. 18, n. 8, p. 692-695, DEC 2016. Web of Science Citations: 6.
MURY, FABIO B.; DA SILVA, WEBER C.; BARBOSA, NADIA R.; MENDES, CAMILA T.; BONINI, JULIANA S.; SOUZA SARKIS, JORGE EDUARDO; CAMMAROTA, MARTIN; IZQUIERDO, IVAN; GATTAZ, WAGNER F.; DIAS-NETO, EMMANUEL. Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer's disease. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 266, n. 7, p. 607-618, OCT 2016. Web of Science Citations: 2.
DUITS, FLORA H.; MARTINEZ-LAGE, PABLO; PAQUET, CLAIRE; ENGELBORGHS, SEBASTIAAN; LLEO, ALBERTO; HAUSNER, LUCREZIA; MOLINUEVO, JOSE L.; STOMRUD, ERIK; FAROTTI, LUCIA; RAMAKERS, INEZ H. G. B.; TSOLAKI, MAGDA; SKARSGARD, CONSTANCE; ASTRAND, RAGNAR; WALLIN, ANDERS; VYHNALEK, MARTIN; HOLMBER-CLAUSEN, MARIE; FORLENZA, ORESTES V.; GHEZZI, LAURA; INGELSSON, MARTIN; HOFF, ERIK I.; ROKS, GERWIN; DE MENDONCA, ALEXANDRE; PAPMA, JANNE M.; IZAGIRRE, ANDREA; TAGA, MARIKO; STRUYFS, HANNE; ALCOLEA, DANIEL A.; FROELICH, LUTZ; BALASA, MIRCEA; MINTHON, LENNART; TWISK, JOS W. R.; PERSSON, STAFFAN; ZETTERBERG, HENRIK; VAN DER FLIER, WIESJE M.; TEUNISSEN, CHARLOTTE E.; SCHELTENS, PHILIP; BLENNOW, KAJ. Performance and complications of lumbar puncture in memory clinics: Results of the multicenter lumbar puncture feasibility study. ALZHEIMERS & DEMENTIA, v. 12, n. 2, p. 154-163, FEB 2016. Web of Science Citations: 53.
FORLENZA, ORESTES V.; APRAHAMIAN, IVAN; RADANOVIC, MARCIA; TALIB, LEDA L.; CAMARGO, MARINA Z. A.; STELLA, FLORINDO; MACHADO-VIEIRA, RODRIGO; GATTAZ, WAGNER F. Cognitive impairment in late-life bipolar disorder is not associated with Alzheimer's disease pathological signature in the cerebrospinal fluid. BIPOLAR DISORDERS, v. 18, n. 1, p. 63-70, FEB 2016. Web of Science Citations: 10.
KERR, DANIEL SHIKANAI; STELLA, FLORINDO; RADANOVIC, MARCIA; APRAHAMIAN, IVAN; FERREIRA BERTOLLUCCI, PAULO HENRIQUE; FORLENZA, ORESTES VICENTE. Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder. BIPOLAR DISORDERS, v. 18, n. 1, p. 71-77, FEB 2016. Web of Science Citations: 5.
FORLENZA, ORESTES V.; APRAHAMIAN, IVAN; DE PAULA, VANESSA J.; HAJEK, TOMAS. Lithium, a Therapy for AD: Current Evidence from Clinical Trials of Neurodegenerative Disorders. Current Alzheimer Research, v. 13, n. 8, p. 879-886, 2016. Web of Science Citations: 16.
STELLA, FLORINDO; FORLENZA, ORESTES VICENTE; LAKS, JERSON; DE ANDRADE, LARISSA PIRES; CACAO, JOAO DE CASTILHO; GOVONE, JOSE SILVIO; DE MEDEIROS, KATE; LYKETSOS, CONSTANTINE G. Caregiver report versus clinician impression: disagreements in rating neuropsychiatric symptoms in Alzheimer's disease patients. INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, v. 30, n. 12, p. 1230-1237, DEC 2015. Web of Science Citations: 12.
TALIB, L. L.; HOTOTIAN, S. R.; JOAQUIM, H. P. G.; FORLENZA, O. V.; GATTAZ, W. F. Increased iPLA2 activity and levels of phosphorylated GSK3B in platelets are associated with donepezil treatment in Alzheimer's disease patients. EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, v. 265, n. 8, p. 701-706, DEC 2015. Web of Science Citations: 12.
DE-PAULA, VANESSA DE JESUS; KERR, DANIEL SHIKANAI; FABIANO DE CARVALHO, MARILIA PALMA; SCHAEFFER, EVELIN LISETE; TALIB, LEDA LEME; GATTAZ, WAGNER FARID; FORLENZA, ORESTES VICENTE. Long-Term Lithium Treatment Increases cPLA(2) and iPLA(2) Activity in Cultured Cortical and Hippocampal Neurons. Molecules, v. 20, n. 11, p. 19878-19885, NOV 2015. Web of Science Citations: 6.
KAMKHAGI, DORLI; OLIVEIRA COSTA, ANA CAROLINA; KUSMINSKY, SANDRA; SUPINO, DEBORAH; DINIZ, BRENO SATLER; GATTAZ, WAGNER FARID; FORLENZA, ORESTES VICENTE. Benefits of psychodynamic group therapy on depression, burden and quality of life of family caregivers to Alzheimer's disease patients. ARCHIVES OF CLINICAL PSYCHIATRY, v. 42, n. 6, p. 157-160, NOV-DEC 2015. Web of Science Citations: 2.
SANTOS, GLENDA DIAS; NUNES, PAULA VILLELA; STELLA, FLORINDO; BRUM, PAULA SCHIMIDT; YASSUDA, MONICA SANCHES; UENO, LINDA MASSAKO; GATTAZ, WAGNER FARID; FORLENZA, ORESTES VICENTE. Multidisciplinary rehabilitation program: effects of a multimodal intervention for patients with Alzheimer's disease and cognitive impairment without dementia. ARCHIVES OF CLINICAL PSYCHIATRY, v. 42, n. 6, p. 153-156, NOV-DEC 2015. Web of Science Citations: 5.
STELLA, FLORINDO; RADANOVIC, MARCIA; CANINEU, PAULO RENATO; DE PAULA, VANESSA J. R.; FORLENZA, ORESTES V. Anti-dementia medications: current prescriptions in clinical practice and new agents in progress. THERAPEUTIC ADVANCES IN DRUG SAFETY, v. 6, n. 4, p. 151-165, AUG 2015. Web of Science Citations: 17.
SCHAEFFER, EVELIN L.; GATTAZ, WAGNER F. Chronic inhibition of brain phospholipase A(2) in adult rats impairs the survival of newborn mature neurons in the hippocampus. JOURNAL OF NEURAL TRANSMISSION, v. 122, n. 5, p. 619-628, MAY 2015. Web of Science Citations: 2.
DE OLIVEIRA, ALEXANDRA MARTINI; RADANOVIC, MARCIA; HOMEM DE MELLO, PATRICIA COTTING; BUCHAIN, PATRICIA CARDOSO; BARBOSA VIZZOTTO, ADRIANA DIAS; CELESTINO, DIEGO L.; STELLA, FLORINDO; PIERSOL, CATHERINE V.; FORLENZA, ORESTES V. Nonpharmacological Interventions to Reduce Behavioral and Psychological Symptoms of Dementia: A Systematic Review. BIOMED RESEARCH INTERNATIONAL, 2015. Web of Science Citations: 39.
FORLENZA, ORESTES VICENTE; MIRANDA, ALINE SILVA; BARBOSA, IZABELA GUIMARAES; TALIB, LEDA LEME; DINIZ, BRENO SATLER; GATTAZ, WAGNER FARID; TEIXEIRA, ANTONIO LUCIO. Decreased Neurotrophic Support is Associated with Cognitive Decline in Non-Demented Subjects. JOURNAL OF ALZHEIMER'S DISEASE, v. 46, n. 2, p. 423-429, 2015. Web of Science Citations: 24.
DINIZ, BRENO S.; TEIXEIRA, ANTONIO L.; MACHADO-VIEIRA, RODRIGO; TALIB, LEDA L.; RADANOVIC, MARCIA; GATTAZ, WAGNER F.; FORLENZA, ORESTES V. Reduced Cerebrospinal Fluid Levels of Brain-Derived Neurotrophic Factor Is Associated With Cognitive Impairment in Late-Life Major Depression. JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES, v. 69, n. 6, p. 845-851, NOV 2014. Web of Science Citations: 30.
MEMORIA, CLAUDIA M.; YASSUDA, MONICA S.; NAKANO, EDUARDO Y.; FORLENZA, ORESTES V. Contributions of the Computer-Administered Neuropsychological Screen for Mild Cognitive Impairment (CANS-MCI) for the diagnosis of MCI in Brazil. INTERNATIONAL PSYCHOGERIATRICS, v. 26, n. 9, p. 1483-1491, SEP 2014. Web of Science Citations: 2.
SCHAEFFER, EVELIN L.; CERULLI, FABIANA G.; SOUZA, HELIO O. X.; CATANOZI, SERGIO; GATTAZ, WAGNER F. Synergistic and additive effects of enriched environment and lithium on the generation of new cells in adult mouse hippocampus. JOURNAL OF NEURAL TRANSMISSION, v. 121, n. 7, p. 695-706, JUL 2014. Web of Science Citations: 4.
FORLENZA, O. V.; DE-PAULA, V. J. R.; DINIZ, B. S. O. Neuroprotective Effects of Lithium: Implications for the Treatment of Alzheimer's Disease and Related Neurodegenerative Disorders. ACS Chemical Neuroscience, v. 5, n. 6, p. 443-450, JUN 2014. Web of Science Citations: 80.
FORLENZA, ORESTES V.; NOVAES COUTINHO, ARTUR MARTINS; APRAHAMIAN, IVAN; PRANDO, SILVANA; MENDES, LUCIANA LUCAS; DINIZ, BRENO S.; GATTAZ, WAGNER F.; BUCHPIGUEL, CARLOS A. Long-Term Lithium Treatment Reduces Glucose Metabolism in the Cerebellum and Hippocampus of Nondemented Older Adults: An [F-18]FDG-PET Study. ACS Chemical Neuroscience, v. 5, n. 6, p. 484-489, JUN 2014. Web of Science Citations: 10.
STELLA, FLORINDO; RADANOVIC, MARCIA; APRAHAMIAN, IVAN; CANINEU, PAULO RENATO; DE ANDRADE, LARISSA PIRES; FORLENZA, ORESTES VICENTE. Neurobiological Correlates of Apathy in Alzheimer's Disease and Mild Cognitive Impairment: A Critical Review. JOURNAL OF ALZHEIMER'S DISEASE, v. 39, n. 3, p. 633-648, 2014. Web of Science Citations: 28.
TALIB, LEDA L.; VALENTE, KETTE D.; VINCENTIIS, SILVIA; GATTAZ, WAGNER F. Correlation between platelet and brain PLA(2) activity. PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, v. 89, n. 4, p. 265-268, SEP 2013. Web of Science Citations: 5.
DINIZ, BRENO S.; TEIXEIRA, ANTONIO L.; MACHADO-VIEIRA, RODRIGO; TALIB, LEDA L.; GATTAZ, WAGNER F.; FORIENZA, ORESTES V. Reduced Serum Nerve Growth Factor in Patients With Late-Life Depression. AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY, v. 21, n. 5, p. 493-496, MAY 2013. Web of Science Citations: 36.
TEIXEIRA, ANTONIO L.; DINIZ, BRENO S.; CAMPOS, ALLINE C.; MIRANDA, ALINE S.; ROCHA, NATALIA P.; TALIB, LEDA L.; GATTAZ, WAGNER F.; FORLENZA, ORESTES V. Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer's Disease. NEUROMOLECULAR MEDICINE, v. 15, n. 1, p. 115-121, MAR 2013. Web of Science Citations: 62.
FORLENZA, ORESTES V.; DINIZ, BRENO S.; STELLA, FLORINDO; TEIXEIRA, ANTONIO L.; GATTAZ, WAGNER F. Mild cognitive impairment (part 1): clinical characteristics and predictors of dementia. Revista Brasileira de Psiquiatria, v. 35, n. 2, p. 178-185, Abr. 2013. Web of Science Citations: 19.
FORLENZA, ORESTES V.; DINIZ, BRENO S.; TEIXEIRA, ANTONIO L.; STELLA, FLORINDO; GATTAZ, WAGNER. Mild cognitive impairment (part 2): biological markers for diagnosis and prediction of dementia in Alzheimer's disease. Revista Brasileira de Psiquiatria, v. 35, n. 3, p. 284-294, Set. 2013. Web of Science Citations: 10.

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