Sex-Specific Protective Effects of APOE epsilon 2 on Cognitive Performance
Por:
Lamonja-Vicente, N, Dacosta-Aguayo, R, Lopez-Oloriz, J, Prades-Senovilla, L, Roig-Coll, F, Castells-Sanchez, A, Soriano-Raya, JJ, Clemente, I, Miralbell, J, Barrios, M, Lopez-Cancio, E, Caceres, C, Arenillas, JF, Millan, M, Toran, P, Pera, G, Fores, R, Alzamora, MT, Mataro, M and Via, M
Publicada:
1 ene 2021
Resumen:
Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE epsilon 2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE epsilon 2 on the normalized values of these cognitive domains occurred only in females (beta = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167-10(-5) and beta = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853.10(-4), respectively). Similarly, the sex-specific effects of APOE epsilon 2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE epsilon 2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE epsilon 2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE epsilon 2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.
Filiaciones:
Lamonja-Vicente, N:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
Dacosta-Aguayo, R:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Lopez-Oloriz, J:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Fdn Josep Finestres FJF, Unidad Trastornos Aprendizaje UTA, Barcelona, Spain
Prades-Senovilla, L:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain
Roig-Coll, F:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Castells-Sanchez, A:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
Soriano-Raya, JJ:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
Clemente, I:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
Miralbell, J:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
Barrios, M:
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
Univ Barcelona, Dept Social Psychol & Quantitat Psychol, Barcelona, Spain
Lopez-Cancio, E:
Unidad Ictus Hosp Univ Cent Asturias HUCA, Dept Neurol, Oviedo, Spain
:
Hosp Badalona Germans Trias & Pujol, Dept Neurosci, Barcelona, Spain
Arenillas, JF:
Hosp Clin Univ, Dept Neurol, Valladolid, Spain
Univ Valladolid, Inst Biol & Genet Mol, Neurovasc Res Lab, CSIC, Madrid, Spain
:
Hosp Badalona Germans Trias & Pujol, Dept Neurosci, Barcelona, Spain
:
FundaciO Inst Univ Recerca AtenciO Primaria Salut, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
Pera, G:
FundaciO Inst Univ Recerca AtenciO Primaria Salut, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
:
FundaciO Inst Univ Recerca AtenciO Primaria Salut, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
:
FundaciO Inst Univ Recerca AtenciO Primaria Salut, Unitat Suport Recerca Metropolitana Nord, Mataro, Spain
Mataro, M:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
Via, M:
Univ Barcelona, Inst Neurociencies, Dept Clin Psychol & Psychobiol, Barcelona, Spain
Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain
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