Paul D. Coleman

A novel technique for the measurement of dielectric and magnetic properties of a homogeneous isotropic medium in the range of approximately 3 to 100 kmc is described. An accuracy of /l.chemc/ 1 per cent is possible in the determination of permittivity or permeability in those cases where the loss tangent is sulliciently small. The measuring structure is a resonator made up of a right circular cyndrical dielectric rod placed between two parallel conducting plates. For measurement of permittivity two or more resonant TE/sub onl/ mode frequencies are determined whereas for the measurement of permeability two or more resonant TM/sub onl/ mode frequencies are determined. The dielectric or magnetic properties are computed from the resonance frequencies, structure dimensions, and unloaded Q. Since the loss tangent is inversely proportional to the unloaded Q of the structure, the precision to which Q is measured determines the accuracy of the loss tangent.

The distinction between the neurodegenerative changes that accompany normal ageing and those that characterise Alzheimer's disease is not clear. The resolution of this issue has important implications for the design of therapeutic and investigative strategies. To this end we have used modern stereological techniques to compare the regional pattern of neuronal cell loss in the hippocampus related to normal ageing to that associated with Alzheimer's disease. The loss related to normal ageing was evaluated from estimates of the total number of neurons in each of the major hippocampal subdivisions of 45 normal ageing subjects who ranged in age from 13 to 101 years. The Alzheimer's disease related losses were evaluated from similar data obtained from 7 cases of Alzheimer's disease and 14 age matched controls. Qualitative differences were observed in the regional patterns of neuronal loss related to normal ageing and Alzheimer's disease. The most distinctive Alzheimer's disease related neuron loss was seen in the CA1 region of the hippocampus. In the normal ageing group there was almost no neuron loss in this region (final neuron count in the CA1 region: 4.40 x 10(6) neurons for the Alzheimer's disease group vs 14.08 x 10(6) neurons in the normal ageing group). It is concluded that the neurodegenerative processes associated with normal ageing and with Alzheimer's disease are qualitatively different and that Alzheimer's disease is not accelerated by ageing but is a distinct pathological process.

We present here a method for broadly characterizing single cells at the molecular level beyond the more common morphological and transmitter/receptor classifications. The RNA from defined single cells is amplified by microinjecting primer, nucleotides, and enzyme into acutely dissociated cells from a defined region of rat brain. Further processing yields amplified antisense RNA. A second round of amplification results in greater than 10(6)-fold amplification of the original starting material, which is adequate for analysis--e.g., use as a probe, making of cDNA libraries, etc. We demonstrate this method by constructing expression profiles of single live cells from rat hippocampus. This profiling suggests that cells that appear to be morphologically similar may show marked differences in patterns of expression. In addition, we characterize several mRNAs from a single cell, some of which were previously undescribed, perhaps due to "rarity" when averaged over many cell types. Electrophysiological analysis coupled with molecular biology within the same cell will facilitate a better understanding of how changes at the molecular level are manifested in functional properties. This approach should be applicable to a wide variety of studies, including development, mutant models, aging, and neurodegenerative disease.

Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea.