Membrane Lipids, Selectively Diminished in Alzheimer Brains, Suggest Synapse Loss as a Primary Event in Early-Onset Form (Type I) and Demyelination in Late-Onset Form (Type II)

Authors

  • Lars Svennerholm,

    Corresponding author
    1. Section of Psychiatry and Neurochemistry, Department of Clinical Neuroscience, University of Göteborg, Göteborg, Sweden
    Search for more papers by this author
  • Carl-Gerhard Gottfries

    1. Section of Psychiatry and Neurochemistry, Department of Clinical Neuroscience, University of Göteborg, Göteborg, Sweden
    Search for more papers by this author

Address correspondence and reprint requests to Dr. L. Svennerholm at Section of Psychiatry and Neurochemistry, Department of Clinical Neuroscience, University of Göteborg, Mölndal Sjukhus, S-431 80 Mölndal, Sweden.

Abstract

Abstract: Major membrane lipids were quantified in frontal (Brodmann area 9) and temporal (Brodmann areas 21 and 22) cortices, caudate nucleus, hippocampus, and frontal white matter of 12 cases with Alzheimer's disease (AD) type I (early onset), 21 cases with AD type II (late onset), and 20 age-matched controls. The concentration of gangliosides—a marker for axodendritic arborization—was reduced to 58–70% of the control concentration in all four gray areas (p < 0.0001) and to 81 % in frontal white matter (p < 0.01) of AD type I cases, whereas it was only significantly reduced in temporal cortex (p < 0.01), hippocampus (p < 0.05), and frontal white matter (p < 0.05) in AD type II cases. The concentration of phospholipids was also significantly reduced (p < 0.01–0.0001) in all four gray areas of AD type I cases but in no area of AD type II cases. The loss of cholesterol was only 50% of the corresponding phospholipid diminution in AD type I. These results suggested a pronounced loss of nerve endings in AD type 1. The characteristic membrane lipid disturbance in AD type II was a loss of myelin lipids. This is the first time a fundamental biochemical difference has been shown between the two major forms of AD.

Ancillary