Initiation and propagation stages of beta-amyloid are associated with distinctive apolipoprotein E, age, and gender profiles.

Several recent studies have defined a relationship between apo-lipoprotein E (apoE) genotype and the risk of various neurodegenerative disorders. However, few studies have examined the influence of apoE on quantitative measures of beta-amyloid (Abeta) accumulation in a large population of autopsy cases. Using a multi-level analysis model, the interrelationships among apoE genotype, gender, age, and Abeta accumulation were investigated. In the population of these cases, there was a strong relationship between the presence of an epsilon4 allele and extent of Abeta in the frontal and entorhinal cortex. That is, when evaluating the presence or absence of significant Abeta (>1% Abeta load), subjects with one and two epsilon4 alleles were 1.9 and 3.5 times more likely to have significant Abeta accumulation than those with no epsilon4 alleles. These risks increased by a multiplicative factor of 1.014 for each year of age (at the time of death). In the subset of cases with significant Abeta (>1% Abeta load), the degree of Abeta load was best predicted by the presence of an epsilon2 allele and gender; females with no epsilon2 alleles had the highest Abeta loads (mean=12.3%), while males with one epsilon2 allele had the lowest amount of Abeta accumulation (mean=8.6%). Our results suggest that the presence of an epsilon4 allele predicts an earlier onset of Abeta deposition that is independent of gender. In contrast, once Abeta deposition has been initiated, the presence of an epsilon2 allele is associated with slower rates of accumulation, with males benefiting from the protective effect more than females.

A learned odor decreases the number of Fos-immunopositive granule cells in the olfactory bulb of young rats.

Olfactory stimulation evokes a column of activity within the olfactory bulb extending from the glomerular layer to the granule cell layer that can be visualized with 2-deoxyglucose autoradiography, optical imaging, Fos protein immunohistochemistry and c-fos mRNA in situ hybridization. The Fos response to odors is typified by the activity of relatively few juxtaglomerular cells, which often occur in foci, and a large number of granule cells extending through much of the bulb. In this study, we characterized the granule cell response to an odor for which young rats had acquired a preference. Fos-like immunoreactive granule cells were quantified by image analysis, and densely stained cells were counted in a region previously shown to be responsive to peppermint odor. We found that odor-trained pups have about half the number of Fos-immunopositive superficial granule cells which respond to a learned odor than do control pups. We then determined whether there was a correlation between the juxtaglomerular cell response and the response of the superficial granule cells deep to those glomerular layer cells. We found a positive correlation between the number of juxtaglomerular cells and the number of granule cells demonstrating Fos immunoreactivity in both control and trained pups, a relationship that changed with early olfactory training.