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Lipid abnormalities in the brain in adult Down’s syndrome and Alzheimer’s disease

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Molecular and Chemical Neuropathology

Abstract

Quantitative analysis by HPTLC of the major lipid classes and dilichol, 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.

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Abbreviations

DS:

Down’s syndrome

PUFA:

Polyunsaturated fatty acyl

SPM:

Sphingomyelin

PE:

Phosphatidylethanolamine

PI:

Phosphatidylinositol

SULF:

Sulfatides

CPG:

Choline phosphoglyceride

SPG:

Serine phosphoglyceride

FAME:

Fatty acid methyl ester

TLC:

Thin-layer chromatography

GLC:

Gas-liquid chromatography

AD:

Alzheimer’s disease

IS:

Internal standard

PC:

Phosphatidylcholine

PS:

Phosphatidylserine

CB:

Cerebrosides

CHOL:

Cholesterol

EPG:

Ethanolamine phosphoglyceride

IPG:

Inositol phosphoglyceride

ChAT:

Choline acetyltransferase

HPTLC:

High-performance thinlayer chromatography

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  1. Medical Research Council External Staff, Department of Clinical Neurology, Institute of Neurology, Wakefield Street, WC1N 1PJ, London, UK

    B. W. L. Brooksbank

  2. Hospital Infantil de la Seguritat Social, Vall d’Hebron, 08035, Barcelona, Spain

    Manuela Martinez

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Brooksbank, B.W.L., Martinez, M. Lipid abnormalities in the brain in adult Down’s syndrome and Alzheimer’s disease. Molecular and Chemical Neuropathology 11, 157–185 (1989). https://doi.org/10.1007/BF03160049

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