Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline

BACKGROUND: Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive. METHODS: In order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia. RESULTS: When considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women. CONCLUSIONS: Altogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches

Migration and urban schistosomiasis. The case of São Lourenço da Mata, Northeast of Brazil Migração e esquistossomose urbana. O caso de São Lourenço da Mata, Nordeste do Brasil

A population-based case-control design was used to investigate the association between migration, urbanisation and schistosomiasis in the Metropolitan Region of Recife, Northeast of Brazil. 1022 cases and 994 controls, aged 10 to 25, were selected. The natives and the migrants who come from endemic areas have a similar risk of infection. On the other hand, the risk of infection of migrants from nonendemic areas seems to be related with the time elapsed since their arrival in São Lourenço da Mata; those who have been living in that urban area for 5 or more years have a risk of infection similar to that of the natives. Those arriving in the metropolitan region of Recife mostly emigrate from "zona da mata" and "zona do agreste" in the state of Pernambuco. Due to the changes in the sugar agro-industry and to the increase in the area used for cattle grazing these workers were driven to villages and cities. The pattern of urbanisation created the conditions for the establishment of foci of transmission in São Lourenço da Mata.<br>Um estudo de caso-controle de base populacional foi desenvolvido para estudar a associação entre migração, urbanização e esquistossomose na Região Metropolitana do Recife, Nordeste do Brasil. Foram selecionados 1022 casos e 994 controles no grupo etário de 10 a 25 anos. Observou-se que os nativos e os migrantes que são provenientes de áreas endêmicas tem um risco semelhante de infecção. Por outro lado, o risco de infecção em migrantes não originários de áreas endêmicas parece estar relacionado com o tempo decorrido desde sua chegada em São Lourenço da Mata; aqueles que estão morando nessa área urbana por um período igual ou superior a cinco anos tem um risco de infeção semelhante ao dos nativos. As mudanças na indústria agro-açucareira na Zona da Mata e a expansão das áreas de criação de gado no Agreste impeliram os trabalhadores rurais a se deslocar para vilarejos e cidades. O padrão de urbanização que ocorreu em São Loureço da Mata criou as condições propícias para que se estabelecessem focos de transmissão