| Grant number: | 15/10109-5 |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| Effective date (Start): | September 01, 2015 |
| Effective date (End): | August 31, 2018 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal researcher: | Maria da Graca Naffah Mazzacoratti |
| Grantee: | Fabricio Ferreira de Oliveira |
| Home 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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