In the present study, modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors by phosphatidylserine (PS) and synaptic plasticity were investigated in the hippocampus of young (4-month-old) and aged (18-month-old) apolipoprotein E (apoE)-deficient mice. Qualitative as well as quantitative analysis of brain sections in both young and aged apoE-deficient mice did not reveal any substantial changes of AMPA receptor binding in the various hippocampal regions, compared to age-matched controls. Nevertheless, enhancement of AMPA receptor binding elicited by PS treatment was found to be abolished in most hippocampal regions of young apoE-deficient mice, while modulation of AMPA receptors by this phospholipid was not significantly altered in the hippocampal formation of aged apoE-deficient animals. At the electrophysiological level, long-term potentiation (LTP) induced by theta burst stimulation was lower in area CA1 of the hippocampus of young, but not aged, apoE-deficient mice compared to age-matched controls. These results confirm that apoE is important for AMPA receptor regulation and LTP expression in the hippocampal formation. However, the presence of LTP in aged apoE-deficient animals, together with apparent recovery of the PS action on AMPA receptors, suggests that aged apoE-knockout mice possess compensatory mechanisms that reduce biochemical and electrophysiological alterations of glutamatergic neurons.

Age Factors↗

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HLA class I, II & III genes in confirmed late-onset Alzheimer's disease.

We first examined all the then known alleles (1997) at the HLA-A, B, Bw, C, DRB1, 3, 4 and 5, and DQB1 loci in 55 late-onset (>65y) AD cases and 73 elderly controls from Oxford. We found an association of HLA-B7 with late-onset AD (odds ratio = 3.1, corrected P = 0.04) that was limited to apolipoprotein E epsilon4-negative subjects (odds ratio = 5.1, corrected P = 0.005). We then studied linkages with Class III genes and, finally, we sought to replicate our HLA-B7 result in cohorts from Montreal and Nottingham. Altogether, we used 299 histopathologically confirmed cases of late-onset AD and 175 controls. Our initial, clear finding was not replicated in Montreal and Nottingham, however. We also failed to support any other previously reported association of AD with an HLA gene. Though we cannot exclude distinct linkages in different cohorts as an explanation of the conflicting results of HLA/AD studies, we conclude that there is no compelling evidence of a strong, direct association between late-onset AD and any HLA Class I or II allele.

Aged↗

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Combined in situ hybridization and immunocytochemistry in the assay of pharmacological effects on tyrosine hydroxylase mRNA concentration.

An assay for tyrosine hydroxylase (TH) mRNA by in situ hybridization in combination with immunocytochemistry (ICC) for TH on the same section is described. The in situ hybridization protocol was optimized for [35S]cRNA (complementary RNA, i.e. anti-sense strand) probe concentration and time of hybridization. The specificity of hybridization was measured by several critera. The advantage of measuring grain density versus grains per cell is discussed for quantitation of in situ autoradiography. Finally, the reserpine-induced increase in adrenal TH mRNA was used to validate quantitative aspects of the in situ hybridization technique by comparison with blot hybridization. In contrast to the adrenal, reserpine did not increase TH mRNA in substantia nigra (s. nigra) neurons as measured by either technique.

Animals↗

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Expert perinatal practice--making a difference.

Explore the source record for details and available documents.

Adult↗

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Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease.

Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon4 by gender, although indicated in the literature, require further verification. A total of 195 past or current control or AD participants in an ongoing longitudinal study of aging and dementia were genotyped. All subjects were at least 60 years old; demented subjects met clinical or pathologic criteria for late-onset AD. Logistic regression analysis and proportional hazard models were used to evaluate joint effects of APOE and gender. A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis. Women carrying one or more APOE-epsilon4 allele were more likely to develop AD [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 3.2-19. 1]. For men, the presence of the APOE-epsilon4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3). The interaction term in the proportional hazards model neared (p = 0.07) statistical significance, and a similar but reduced gender effect was shown. The analysis suggests that the presence of one or more APOE-epsilon4 allele confers a substantially greater risk of AD to women than to men. These findings in part may account for reports of increased risk of AD faced by women.

Aged↗