Abstract— In the ‘Quaking’ mouse, a deficiency in the long chain fatty acid content of galactolipids has been shown to occur. Myelin in the mutant has been compared to myelin in adult and in 12‐day‐old controls. We have shown that myelin is not only quantitatively reduced but also qualitatively modified, with a higher protein and a lower galactolipid content. Cerebrosides contain only a small amount of kerasin, lacking long chain nonhydroxylated fatty acids in comparison to both controls; the relative percentage of phrenosin is increased. Although many similarities exist between adult Quaking myelin and myelin at 12 days, differences have been shown to occur which may be in relation to a genetic block at an earlier stage of development.

The "Quaking" mouse is a recessive autosomal mutant characterized by a deficient myelination of the central nervous system.The disease is recognized at about the twelfth day after birth and reaches its full expression by about three weeks. The animal has an unsteady gait and a marked tremor of the hind quarters; epileptic fits are induced by sensory stimulations a t the adult age. This mutation apparently involves the process of myelin formation; there is no evidence of destruction. The analysis of brain fatty acids and lipids was undertaken to find out if the inyelin deficiency involves an inborn error in the metabolism of one of its major constituents. "Quaking" males aged from seven to ten weeks were compared to apparently normal litter-mates. At this stage, myelination is achieved. Brain lipids are diminished, especially galactolipids. Qualitative modifications of cerebrosides, sphingomyelin and sulphatides have been detected by mono and two dimensional thin layer chromatography. The proportion of long chain fatty acids (especially CZ4) is greatly diminished, as shown by gas chromatography. This is true for both cerebrosides and sphingomyelin.I n conclusion, the long chain fatty acids of galactolipids and sphingomyelin are considerably diminished in the "Quaking" mouse. Whether it is a cause or a consequence of myelination deficiency remains to be proved, although the importance of the alteration is in favour of the first hypothesis.Sidman et al. [I] were the first to describe the recessive and autosomal "Quaking" mutation observed in 1961 at the Jackson Laboratory[2] in strain DBA of the black mouse. It is characterized by an impairment in myelin formation of the central nervous system.The disease is recognized at about the twelfth day after birth and reaches its full expression by about three weeks. The animal has an unsteady gait and a marked tremor of the hind quarters; epileptic fits are induced by sensory stimulations at the adult age.The entire central nervous system is considerably deficient in myelin [l]; however, some fragments of myelin are present in almost all tracts. There is no evidence of destruction, no globoid cells, no metachromatic lipids and no inflammation ; the neurons, the axons, the glial cells appear normal, as well as myelin of the peripheral nervous system.Non-Standard Abbreviations. Fatty acids are identified by the carbon number and number of double bonds (18:O = stearic acid); h indicates the presence of a 2-hydroxy group.

The aim of this study was to compare brain glial fibrillary acidic protein (GFAP) levels to the modifications of cognitive functions (Blessed test score [BTS]), the density of the main neuropathological lesions (senile plaques [SP] and neurofibrillary tangles [NFT]), and the density of the two main subtypes of beta A4 deposits (classic plaques and diffuse deposits) in a series of patients with normal aging and senile dementia of the Alzheimer type of various degrees of severity. GFAP levels (enzyme-linked immunosorbent assay [ELISA] technique) and the densities of changes were measured in the temporal lobe of 12 women over 75 years of age. Under these conditions, the ELISA assay could determine GFAP in brain homogenates (aqueous-Triton buffer soluble extract) in a range from 2.5 ng to 600 ng per assay. Least affected patients (with a BTS of 19 and over) all ranged below 60 micrograms/mg protein. Most affected patients (with a BTS under 6) ranged above 150 micrograms/mg protein. However, interindividual variations were wide. A significant correlation between the BTS and the amount of GFAP could be found only when using the non parametric test of Spearman. There was a significant positive correlation between the amount of GFAP and the density of 1) SP, 2) NFT both revealed by Bodian's silver stain, and 3) classic beta A4 plaques shown by immunocytochemistry. On the contrary, no correlation was observed with diffuse beta A4 deposits. One case with very large amounts of diffuse beta A4 deposits without SP or NFT showed no associated GFAP reactivity. This suggests that GFAP production is a critical event in the formation of classic SP.

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