Factors determining the size frequency distribution of beta-amyloid (A beta) deposits in Alzheimer's disease

The size frequency distributions of discrete beta-amyloid (A beta) deposits were studied in single sections of the temporal lobe from patients with Alzheimer's disease. The size distributions were unimodal and positively skewed. In 18/25 (72%) tissues examined, a log normal distribution was a good fit to the data. This suggests that the abundances of deposit sizes are distributed randomly on a log scale about a mean value. Three hypotheses were proposed to account for the data: (1) sectioning in a single plane, (2) growth and disappearance of A beta deposits, and (3) the origin of A beta deposits from clusters of neuronal cell bodies. Size distributions obtained by serial reconstruction through the tissue were similar to those observed in single sections, which would not support the first hypothesis. The log normal distribution of A beta deposit size suggests a model in which the rate of growth of a deposit is proportional to its volume. However, mean deposit size and the ratio of large to small deposits were not positively correlated with patient age or disease duration. The frequency distribution of A beta deposits which were closely associated with 0, 1, 2, 3, or more neuronal cell bodies deviated significantly from a log normal distribution, which would not support the neuronal origin hypothesis. On the basis of the present data, growth and resolution of A beta deposits would appear to be the most likely explanation for the log normal size distributions.