JOSE MARCELO FARFEL
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Ortopediae Traumatologia, Faculdade de Medicina - Docente
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
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- APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults(2019) LAMAR, Melissa; YU, Lei; RUBIN, Leah H.; JAMES, Bryan D.; BARNES, Lisa L.; FARFEL, Jose Marcelo; GAITERI, Chris; BUCHMAN, Aron S.; BENNETT, David A.; SCHNEIDER, Julie A.Introduction: Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology. Methods: We investigated associations of APOE status with arteriolosclerosis, macroinfarcts and microinfarcts, and atherosclerosis in 1383 adults (65.9-108.2 years at death) with and without dementia. Excluding epsilon 2/epsilon 4 carriers, multivariable regressions for each CVD-related neuropathology compared epsilon 4 and epsilon 2 carriers to epsilon 3/epsilon 3 carriers adjusting for confounders including age and Alzheimer's neuropathology. Results: Three hundred forty-two individuals (24.7%; similar to 87.7 years at death; 39.9% nondemented) were epsilon 3/epsilon 4 or epsilon 4/epsilon 4, and 180 (13.0%; similar to 89.9 years at death; 66.6% nondemented) were epsilon 2/epsilon 3 or epsilon 2/epsilon 2. epsilon 4 carriers had higher odds of macroinfarcts (odds ratio = 1.41, 95% confidence interval: 1.02-1.94, P = .03), whereas epsilon 2 carriers had higher odds of moderate-to-severe arteriolosclerosis (odds ratio = 1.68, 95% confidence interval: 1.15-2.45, P = .006) compared to e3/e3 carriers. Age-stratified analyses suggested that these relationships were driven by epsilon 4 carriers <90 years at death and epsilon 2 carriers >= 90 years at death, respectively. Discussion: APOE differentially affects type and timing of CVD-related neuropathology.
- Neuropathologic features of TOMM40 ' 523 variant on late-life cognitive decline(2017) YU, Lei; LUTZ, Michael W.; FARFEL, Jose M.; WILSON, Robert S.; BURNS, Daniel K.; SAUNDERS, Ann M.; JAGER, Philip L. De; BARNES, Lisa L.; SCHNEIDER, Julie A.; BENNETT, David A.Introduction: The study investigated the role of neuropathologies in the relationship between TOMM40' 523 genotype and late-life cognitive decline. Methods: Participants were community-dwelling older persons who had annual cognitive assessments and brain autopsies after death. Genotyping used DNA from peripheral blood or postmortem brain tissue. Linear mixed models assessed the extent to which the association of '523 genotype with cognitive decline is attributable to neuropathologies. Results: Relative to epsilon 3/epsilon 3 homozygotes with '523-S/VL or '523-VL/VL genotype, both '523-L carriers and epsilon 3/epsilon 3 homozygotes with '523-S/S genotype had faster cognitive decline. The association of '523-L with cognitive decline was attenuated and no longer significant after controlling for Alzheimer's and other neuropathologies. By contrast, the association of '523-S/S was unchanged. Discussion: There are two distinct TOMM40' 523 signals in relation to late-life cognitive decline. One signal primarily acts through AD and other common neuropathologies, whereas the other operates through a different mechanism.