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Comparative analysis of cerebrospinal fluid and serum markers in dementia with Lewy Bodies and Alzheimer's Disease dementia

Grant number: 15/10109-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): September 01, 2015
Effective date (End): August 31, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Maria da Graca Naffah Mazzacoratti
Grantee:Fabricio Ferreira de Oliveira
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The objective of this cross-sectional study consists on the comparative analysis of cerebrospinal fluid and serum biomarkers among controls without dementia, patients with dementia with Lewy bodies, and patients with probable Alzheimer's disease dementia, seeking to better discriminate between these dementia syndromes and contrast with people without cognitive impairment. At least 26 subjects with dementia with Lewy bodies will be paired with 26 subjects with probable Alzheimer's disease dementia by gender and cognitive scores, also paired with 26 controls without dementia by gender and age (±1 year). All subjects and controls will undergo blood tests for genetic definition of APOE haplotypes, protein electrophoresis, and measurement of concentration and activity of the angiotensin-converting enzyme. All subjects and controls will also be submitted to cerebrospinal fluid cytometry, in addition to analyses of concentrations of total proteins and protein fractions, Abeta42, Abeta40, Abeta38, tau, phosphorilated tau, alpha-synuclein, ubiquitin, monoamine metabolites (HVA, DOPAC, 5-HIAA, MHPG), and measurement of concentration and activity of the angiotensin-converting enzyme. The study of the cognitive effects of the angiotensin-converting enzyme is justified by its peripheral actions over secretion of adipocytokines and glucose homeostasis, as well as its central actions over degradation of Abeta and brain substance P, thus reducing the activity of neprilysin (which is also an Abeta-degrading enzyme) and the Abeta42/Abeta40 index. Whereas the activity of angiotensin-converting enzyme is boosted in the presence of Abeta, angiotensin-converting enzyme inhibitors might slow cognitive decline by way of central mechanisms and cerebrovascular benefits, particularly when these drugs are brain-penetrating and centrally acting. After controlling for APOE haplotypes and specific pharmacological treatment, it is expected that these biomarkers as well as the relations amongst them might help in the differential diagnoses among dementia syndromes and absence of dementia, in the definition of specific dementia stages, in the determination of patterns of cognitive and functional decline, in the correlation with neuropsychiatric symptoms, and in the detection of mechanisms of amyloidogenesis. (AU)

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Scientific publications (25)
(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)
FABRICIO F. DE OLIVEIRA; ELIZABETH S. CHEN; MARILIA C. SMITH; PAULO H. BERTOLUCCI. Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer's disease dementia. Revista Brasileira de Psiquiatria, v. 39, n. 2, p. 95-103, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; MACHADO, FERNANDO CHIODINI; SAMPAIO, GUSTAVO; CORREIA MARIN, SHEILLA DE MEDEIROS; NAFFAH-MAZZACORATTI, MARIA DA GRACA; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Neuropsychiatric feature profiles of patients with Lewy body dementia. CLINICAL NEUROLOGY AND NEUROSURGERY, v. 194, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Longitudinal lipid profile variations and clinical change in Alzheimer's disease dementia. Neuroscience Letters, v. 646, p. 36-42, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; DE ALMEIDA, SANDRO SOARES; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; NAFFAH-MAZZACORATTI, MARIA DA GRACA; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Lifetime Risk Factors for Functional and Cognitive Outcomes in Patients with Alzheimer's Disease. JOURNAL OF ALZHEIMER'S DISEASE, v. 65, n. 4, p. 1283-1299, . (15/10109-5)
OLIVEIRA, FABRICIO FERREIRA DE; DE ALMEIDA, SANDRO SOARES; SMITH, MARILIA CARDOSO; BERTOLUCCI, PAULO HENRIQUE FERREIRA. Behavioural effects of the ACE insertion/deletion polymorphism in Alzheimer's disease depend upon stratification according to APOE-epsilon 4 carrier status. COGNITIVE NEUROPSYCHIATRY, v. 26, n. 4, p. 293-305, . (15/18125-0, 15/10109-5)
SILVA, NARLON C. BOA SORTE; BRACKO, OLIVER; NELSON, AMY R.; DE OLIVEIRA, FABRICIO FERREIRA; ROBISON, LISA S.; SHAABAN, C. ELIZABETH; HAINSWORTH, ATTICUS H.; PRICE, BRITTANI R.. Vascular cognitive impairment and dementia: An early career researcher perspective. ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING, v. 14, n. 1, p. 13-pg., . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; MIRALDO, MARJORIE CAMARA; DE CASTRO-NETO, EDUARDO FERREIRA; DE ALMEIDA, SANDRO SOARES; DE ANDRADE MATAS, SANDRO LUIZ; FERREIRA BERTOLUCCI, PAULO HENRIQUE; NAFFAH-MAZZACORATTI, MARIA DA GRACA. Associations of Neuropsychiatric Features with Cerebrospinal Fluid Biomarkers of Amyloidogenesis and Neurodegeneration in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People. JOURNAL OF ALZHEIMER'S DISEASE, v. 81, n. 3, p. 1305-1319, . (15/18125-0, 15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; MIRALDO, MARJORIE CAMARA; DE CASTRO-NETO, EDUARDO FERREIRA; DE ALMEIDA, SANDRO SOARES; MATAS, SANDRO LUIZ DE ANDRADE; BERTOLUCCI, PAULO HENRIQUE FERREIRA; NAFFAH-MAZZACORATTI, MARIA DA GRACA. Differential associations of clinical features with cerebrospinal fluid biomarkers in dementia with Lewy bodies and Alzheimer's disease. AGING CLINICAL AND EXPERIMENTAL RESEARCH, v. N/A, p. 12-pg., . (15/10109-5, 15/18125-0)
AGUERA-ORTIZ, LUIS; BABULAL, GANESH M.; BRUNEAU, MARIE-ANDREE; CREESE, BYRON; D'ANTONIO, FABRIZIA; FISCHER, CORINNE E.; GATCHEL, JENNIFER R.; ISMAIL, ZAHINOOR; KUMAR, SANJEEV; MCGEOWN, WILLIAM J.; et al. Psychosis as a Treatment Target in Dementia: A Roadmap for Designing Interventions. JOURNAL OF ALZHEIMER'S DISEASE, v. 88, n. 4, p. 26-pg., . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; ALMEIDA, SANDRO SOARES DE; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; BERTOLUCCI, PAULO HENRIQUE FERREIRA. Pharmacogenetics of angiotensin modulators according to APOE-ε4 alleles and the ACE insertion/deletion polymorphism in Alzheimer's disease. ACTA NEUROPSYCHIATRICA, v. N/A, p. 16-pg., . (15/10109-5)
DE OLIVEIRA, FABRICIO F.; CHEN, ELIZABETH S.; SMITH, MARILIA C.; BERTOLUCCI, PAULO H.. Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer's disease dementia. Revista Brasileira de Psiquiatria, v. 39, n. 2, p. 9-pg., . (15/10109-5)
OLIVEIRA, F. F.; ALMEIDA, G. V., JR.; ALMEIDA, S. S.; CHEN, E. S.; SMITH, M. A. C.; BERTOLUCCI, P. H. F.. Pharmacogenetics of angiotensin receptor blockers in patients with dementia due to Alzheimer's disease. EUROPEAN JOURNAL OF NEUROLOGY, v. 24, p. 1-pg., . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; CORREIA MARIN, SHEILLA DE MEDEIROS; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Neurological impressions on the organization of language networks in the human brain. BRAIN INJURY, v. 31, n. 2, p. 140-150, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; PEREIRA, FERNANDO VIEIRA; KAMIKADO PIVI, GLAUCIA AKIKO; SMITH, MARILIA CARDOSO; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Effects of APOE haplotypes and measures of cardiovascular risk over gender-dependent cognitive and functional changes in one year in Alzheimer's disease. International Journal of Neuroscience, v. 128, n. 5, p. 472-476, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; BERRETTA, JULIANA MARILIA; DE ALMEIDA JUNIOR, GUIDO VEIGA; DE ALMEIDA, SANDRO SOARES; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia. INDIAN JOURNAL OF MEDICAL RESEARCH, v. 150, n. 3, p. 261-271, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease. DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, v. 41, n. 5-6, p. 314-323, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia. Current Alzheimer Research, v. 15, n. 4, p. 386-398, . (15/18125-0, 15/10109-5)
FABRICIO F. DE OLIVEIRA; ELIZABETH S. CHEN; MARILIA C. SMITH; PAULO H. BERTOLUCCI. Associations of cerebrovascular metabolism genotypes with neuropsychiatric symptoms and age at onset of Alzheimer’s disease dementia. Revista Brasileira de Psiquiatria, v. 39, n. 2, p. 95-103, . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; FERREIRA BERTOLUCCI, PAULO HENRIQUE; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO. Pharmacogenetic Analyses of Therapeutic Effects of Lipophilic Statins on Cognitive and Functional Changes in Alzheimer's Disease. JOURNAL OF ALZHEIMER'S DISEASE, v. 87, n. 1, p. 14-pg., . (15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; FERREIRA BERTOLUCCI, PAULO HENRIQUE. Selected LDLR and APOE Polymorphisms Affect Cognitive and Functional Response to Lipophilic Statins in Alzheimer's Disease. JOURNAL OF MOLECULAR NEUROSCIENCE, v. 70, n. 10, . (15/18125-0, 15/10109-5)
DE OLIVEIRA, FABRICIO FERREIRA; DE ALMEIDA, SANDRO SOARES; CHEN, ELIZABETH SUCHI; SMITH, MARILIA CARDOSO; BERTOLUCCI, PAULO HENRIQUE FERREIRA. APOE ε4 Carrier Status as Mediator of Effects of Psychotropic Drugs on Clinical Changes in Patients With Alzheimer's Disease. JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES, v. 34, n. 4, p. 10-pg., . (15/10109-5, 15/18125-0)
DE OLIVEIRA, FABRICIO; MIRALDO, MARJORIE; CASTRO-NETO, EDUARDO; MACHADO, FERNANDO; ALMEIDA, SANDRO; MATAS, SANDRO; BERTOLUCCI, PAULO; NAFFAH-MAZZACORATTI, MARIA. Behavioral correlates of cerebrospinal fluid concentrations of aminoacids and monoamine metabolites according to APOE-epsilon 4 carrier status in dementia with Lewy bodies compared with Alzheimer's dementia and cognitively healthy people. Neurology, v. 90, p. 2-pg., . (15/10109-5)
BATEMAN, DANIEL R.; GILL, SASCHA; HU, SOPHIE; FOSTER, ERIN D.; RUTHIRAKUHAN, MYURI T.; SELLEK, ALLIS F.; MORTBY, MOYRA E.; MATUSKOVA, VERONIKA; NG, KOK PIN; TARAWNEH, RAWAN M.; et al. Agitation and impulsivity in mid and late life as possible risk markers for incident dementia. ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS, v. 6, n. 1, p. 22-pg., . (15/10109-5)
OLIVEIRA, F. F.; MIRALDO, M. C.; MACHADO, F. C.; ALMEIDA, S. S.; MATAS, S. L. A.. Motor aspects of daily living are inversely associated with anxiety and dysphoria in Parkinson's disease dementia but not in dementia with Lewy bodies. EUROPEAN JOURNAL OF NEUROLOGY, v. 24, p. 2-pg., . (15/10109-5)
OLIVEIRA, F. F.; ALMEIDA JUNIOR, G. V.; ALMEIDA, S. S.; BERTOLUCCI, P. H. F.. APOE haplotypes modify the associations of the ACE insertion/deletion polymorphism with neuropsychiatric symptoms in dementia due to Alzheimer's disease. EUROPEAN JOURNAL OF NEUROLOGY, v. 24, p. 1-pg., . (15/10109-5)

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