Gender modulates the APOE ε4 effect in healthy older adults: convergent evidence from functional brain connectivity and spinal fluid tau levels.
ABSTRACT We examined whether the effect of the apolipoprotein E (APOE) genotype on functional brain connectivity is modulated by gender in healthy older human adults. Our results confirm significantly decreased connectivity in the default mode network in healthy older APOE ε4 carriers compared with ε3 homozygotes. More important, further testing revealed a significant interaction between APOE genotype and gender in the precuneus, a major default mode hub. Female ε4 carriers showed significantly reduced default mode connectivity compared with either female ε3 homozygotes or male ε4 carriers, whereas male ε4 carriers differed minimally from male ε3 homozygotes. An additional analysis in an independent sample of healthy elderly using an independent marker of Alzheimer's disease, i.e., spinal fluid levels of tau, provided corresponding evidence for this gender-by-APOE interaction. Together, these results converge with previous work showing a higher prevalence of the ε4 allele among women with Alzheimer's disease and, critically, demonstrate that this interaction between APOE genotype and gender is detectable in the preclinical period.
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ABSTRACT: Micrometastasis are defined by the existence of cells or groups of cells in target organs. In the particular cas of colon cancers, although lymph node involvement is frequent, metastatic medullary involvement (while rarely at the origin of identified metastasis) can also be observed. Furthermore, micrometastatics cells can be identified in the circulating blood. This research relies on recent technics of immunocytochemistry with image analysis or molecular biology technics (generally PCR or RT-PCR). It is essential to have a specific reliable marker of metastatic cells. The prognostic value of identifying micrometastasis in organs also remains to be defined.Journal de Chirurgie 07/2002; 139(3):141-8. · 0.50 Impact Factor
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ABSTRACT: Associations between postmenopausal hormone therapy (HT) and cognitive decline may depend on apolipoprotein E (APOE) status or timing of initiation. We included 16,514 Nurses' Health Study participants aged 70-81 years who were followed since 1976 and completed up to 3 telephone cognitive assessments (2 years apart), between 1995 and 2006. The tests assessed general cognition (Telephone Interview of Cognitive Status; TICS), verbal memory, and category fluency. We used longitudinal analyses to estimate differences in cognitive decline across hormone groups. APOE genotype was available in 3697 participants. Compared with never users, past or current HT users showed modest but statistically significant worse rates of decline in the TICS: the multivariable-adjusted difference in annual rate of decline in the TICS among current estrogen only users versus never users was -0.04 (95% confidence interval, -0.07 to -0.004); for current estrogen + progestin users, the mean difference was -0.05 (95% confidence interval, -0.10 to -0.002). These differences were equivalent to those observed in women who are 1-2 years apart in age. We observed no protective associations with early timing of hormone initiation. We found suggestive interactions with APOE e4 status (e.g., on TICS, p interaction, 0.10), where the fastest rate of decline was observed among APOE e4 carriers who were current HT users. Regardless of timing of initiation, HT may be associated with worse rates of decline in general cognition, especially among those with an APOE e4 allele.Neurobiology of aging 11/2010; 33(7):1129-37. · 5.94 Impact Factor
Article: Facial sweat gland carcinoma metastasizing to neck nodes: a diagnostic and therapeutic challenge.[show abstract] [hide abstract]
ABSTRACT: We report an unusual case involving a patient with sweat gland carcinoma of the cheek who presented with ipsilateral neck lymph node metastasis 10 years after his initial presentation. Pathological analysis of the surgical specimen revealed a strong reactivity of tumor cells to gross cystic disease fluid protein 15, estrogen receptor protein, and progesterone receptor protein. On the basis of these results, tamoxifen citrate therapy was initiated empirically. Our patient has been disease free for more than 3 years. Based on this and another case reported in the literature, we believe that antiestrogen therapy could prove beneficial in a subset of patients with sweat gland carcinoma. We recommend future multicenter clinical trials to assess the effectiveness of postoperative tamoxifen therapy for patients with estrogen and progesterone receptor protein-positive metastatic sweat gland carcinoma.Archives of Otolaryngology - Head and Neck Surgery 01/2002; 127(12):1495-8. · 1.63 Impact Factor