Association between lobar microbleeds, CSF amyloid-beta, and epsilon-4 APOE allele in patients with dementia due to Alzheimer's Disease and mild cognitive impairment

• Grant number: 14/25429-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2015
• Effective date (End): May 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcio Luiz Figueredo Balthazar
• Grantee: Ana Gabriela Bicalho Rabelo
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/17092-0 - Biomarkers in Alzheimer's Disease and mild cognitive impairment: evaluation of functional magnetic resonance imaging methods, plasmatic and cerebrospinal fluid markers, AP.JP

Abstract

Dementia due to Alzheimer's disease (AD) is a neurodegenerative disease that impacts the individual's cognition, behavior, and functional independence. It shows alarming incidence and prevalence numbers, coming to be a growing problem for the public health system. The main genetic risk factor for developing AD is the epsilon-4 apolipoprotein E (APOE) allele. The central hypothesis towards understanding the interaction between different isoforms of APOE and AD is its influence on amyloid-beta (AB) metabolism. AB is one of the key components in AD physiopathological events. It may accumulate in the intravascular wall compartment in cerebral amyloid angiopathy (CAA), being an important cause of lobar microbleeds. Most cases of CAA also show the presence of neuritic plaques (senile plaques), both being a result of AB accumulating in the brain. Therefore, lobar microbleeds associated with CAA could possibly come to be an important indicator of neuritic plaques, a physiopathological characteristic of AD. Comes into question a possible association of AD and amnestic mild cognitive impairment (aMCI) to amounts of lobar microbleeds, to AB liquoric levels as a result of AB accumulation in the brain, and to the presence of APOE epsilon-4 allele. In the present study, we aim to investigate the following hypotheses: 1) These variables (amounts of lobar microbleeds, AB liquoric levels, and the presence of APOE epsilon-4 allele) are related to each other in AD and in aMCI; 2) The number of lobar microbleeds in AD and in aMCI are inversely proportional to AB liquoric levels, especially in patients with APOE µ4 allele; 3) If the number of lobar microbleeds are able to separate patients with mild AD, patients with aMCI and healthy elderly individuals. 90 subjects will be included in this study: 30 healthy elderly individuals, 30 mild AD and30 aMCI patients matched by sex, age, and cardiovascular risk factors (arterial systemic hypertension, diabetes, dyslipidemia, smoking habits). All subjects will undergo neuropsychological assessment, cerebrospinal fluid and blood samples, as well as brain MRI at 3 Tesla to evaluate microbleeds. (AU)

Scientific publications

(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)

RABELO, ANA G. B.; TEIXEIRA, CAMILA V. L.; MAGALHAES, THAMIRES N. C.; CARLETTI-CASSANI, ANA FLAVIA M. K.; AMATO FILHO, AUGUSTO C. S.; JOAQUIM, HELENA P. G.; TALIB, LEDA L.; FORLENZA, ORESTES; RIBEIRO, PATRICIA A. O.; SECOLIN, RODRIGO; et al. Is cerebral microbleed prevalence relevant as a biomarker in amnestic mild cognitive impairment and mild Alzheimer's disease?. NEURORADIOLOGY JOURNAL, v. 30, n. 5, p. 477-485, OCT 2017. (13/07559-3, 14/25429-2)