Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome).

The discovery that the epsilon 4 allele of the apolipoprotein E (apoE) gene is a putative risk factor for Alzheimer disease (AD) in the general population has highlighted the role of genetic influences in this extremely common and disabling illness. It has long been recognized that another genetic abnormality, trisomy 21 (Down syndrome), is associated with early and severe development of AD neuropathological lesions. It remains a challenge, however, to understand how these facts relate to the pathological changes in the brains of AD patients. We used computerized image analysis to examine the size distribution of one of the characteristic neuropathological lesions in AD, deposits of A beta peptide in senile plaques (SPs). Surprisingly, we find that a log-normal distribution fits the SP size distribution quite well, motivating a porous model of SP morphogenesis. We then analyzed SP size distribution curves in genotypically defined subgroups of AD patients. The data demonstrate that both apoE epsilon 4/AD and trisomy 21/AD lead to increased amyloid deposition, but by apparently different mechanisms. The size distribution curve is shifted toward larger plaques in trisomy 21/AD, probably reflecting increased A beta production. In apoE epsilon 4/AD, the size distribution is unchanged but the number of SP is increased compared to apoE epsilon 3, suggesting increased probability of SP initiation. These results demonstrate that subgroups of AD patients defined on the basis of molecular characteristics have quantitatively different neuropathological phenotypes.

Beryllium-10, mineralogy and grain size distribution of DSDP Hole 68-502B (Table 1)

We present a high-resolution 10Be profile from deep sea sediments (sampled from Hole 502B in the Caribbean sea) that strongly resembles the 10Be record in ice core profiles, particularly the Vostok core from Antarctica. This high-resolution profile revealed occurrences of enhanced 10Be concentrations at about 23-24, 37-39 and 60-65 ka. The excellent match between these peaks appearing in a georeservoir profile other than in polar ice, strengthens the implications that can be inferred from 10Be and provide global markers for chronological correlation of climatic events. The position at low latitude of the studied sediment section is, unlike the case with the high latitude polar regions, excellent for exposing causes of modulation in 10Be production. We interpret the source of the pattern and enhancements, particularly the 37-39 ka peak, of 10Be to be global and do not strictly relate to climatic conditions and/or production rates specific to the polar regions.