dolichols and Down-Syndrome

Quantitative analysis by HPTLC of the major lipid classes and dolichol, and of fatty acyl groups of separated phosphoglycerides by capillary GLC, has been carried out on the gray matter of frontal cerebral cortex of brains from six Down's syndrome (DS) and six Alzheimer's disease (AD) adults, and six each of two corresponding sets of age-matched controls; specimens of DS and control cerebellum and corpus callosum were also analyzed. In DS frontal cortex, but not in AD frontal cortex, compared to their respective controls there was a decrease in the fraction of phosphatidylethanolamine (PE) and an increase in the fractions of sphingomyelin (SPM) and phosphatidylserine (PS). Abnormalities were not found in the proportions of major lipid classes in DS cerebellum or corpus callosum. The concentration of dolichol was elevated for age in the frontal cortex of DS and of AD. In the phosphoglycerides of DS frontal cortex, the fatty acyl composition showed small, but statistically significant, differences from those of age-matched controls, and some slight abnormalities were also detected in DS corpus callosum. The alterations in DS frontal cortex included decreases in (n-6) and increases in (n-3) groups in choline and ethanolamine phosphoglycerides (CPG and EPG), as had previously been found in EPG and serine phosphoglyceride (SPG) of the DS fetal brain. In DS frontal cortex, the proportion of 22:4(n-6) groups was decreased in SPG, and in inositol phosphoglyceride (IPG) 18:1(n-9) was increased. There were also small but significant alterations in DS frontal cortex in the fractions of shorter chain groups in CPG. In marked contrast, most of the fatty acyl abnormalities seen in DS were absent in the AD frontal cortex. It is therefore suggested that some abnormalities in the composition of cerebral membranes present prenatally in DS may persist into adulthood, and are not directly related to AD-type pathology.

Topics: Acetals; Aged; Aged, 80 and over; Alzheimer Disease; Brain Chemistry; Cerebellum; Choline O-Acetyltransferase; Chromatography, Gas; Corpus Callosum; Dolichols; Down Syndrome; Esters; Fatty Acids; Frontal Lobe; Glycerophosphates; Humans; Lipids; Methanol; Middle Aged; Phospholipids

Long-chain polyisoprenoid alcohols (dolichols) were measured in different brain regions dissected postmortem from 26 histopathologically confirmed cases of Alzheimer's disease and 24 age-matched nonAlzheimer control patients. They were significantly elevated in all parts of the cerebrum, but not in the cerebellum, of Alzheimer patients. The highest values were found in the temporal cortex and hippocampus. Out of the individual dolichol molecular species, the one with the most isoprene units (C105) was significantly increased in the temporal cortex, hippocampus, and basal forebrain of Alzheimer patients, compared with the controls. Dolichols were normal in the urinary sediment of 10 Alzheimer patients and nine patients with Down's syndrome, in comparison to age-matched controls for both groups. This is in contrast to neuronal ceroid-lipofuscinosis patients in whom dolichols are elevated in cerebral cortex, as well as in the cells of the urinary sediment, indicating generalized ceroid-lipofuscin storage.

Topics: Aged; Alzheimer Disease; Brain; Diterpenes; Dolichols; Down Syndrome; Humans; Middle Aged