[Lipid rafts, flotillin-1 and Alzheimer disease].
A beta peptide accumulates in the extracellular space during Alzheimer's disease. It is the cleavage product of APP (Amyloid Precursor Protein), a large transmembrane protein. After ultracentrifugation, APP is found in a low-density fraction, enriched in cholesterol. These properties are characteristic of lipid rafts, which are microdomains that "float" like rafts on the plasma membrane. We have confirmed the presence of cholesterol in the core of the senile plaque, using the fluorescent probe filipin. In addition, we have shown that flotillin-1, a marker of rafts, accumulated in lysosomes of neurons in Alzheimer's disease. In most cases (76% of the flotillin-1 positive neurons), the accumulation was associated with the presence of neurofibrillary tangles. Our data suggest that the A beta peptide, which is poorly soluble in water, is actually linked with cholesterol, possibly from cellular membranes, in the extracellular space.
Girardot
Nadège
N
Laboratoire de Neuropathologie Raymond Escourolle et Inserm U106, Hôpital de La Salpêtrière, Paris.
Allinquant
Bernadette
B
Duyckaerts
Charles
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D015415:Biomarkers; D002540:Cerebral Cortex / Q000473:pathology; D006801:Humans; D008247:Lysosomes / Q000473:pathology / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000473:pathology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000032:analysis*; D009474:Neurons / Q000473:pathology
D015415:Biomarkers; D008565:Membrane Proteins; C106354:flotillins