Characterization of detergent-insoluble complexes containing the familial Alzheimer's disease-associated presenilins

J Neurochem. 1999 Apr;72(4):1534-43. doi: 10.1046/j.1471-4159.1999.721534.x.


Many cases of early-onset familial Alzheimer's disease have been linked to mutations within two genes encoding the proteins presenilin-1 and presenilin-2. The presenilins are 48-56-kDa proteins that can be proteolytically cleaved to generate an N-terminal fragment (approximately 25-35 kDa) and a C-terminal fragment (approximately 17-20 kDa). The N- and C-terminal fragments of presenilin-1, but not full-length presenilin-1, were readily detected in both human and mouse cerebral cortex and in neuronal and glioma cell lines. In contrast, presenilin-2 was detected almost exclusively in cerebral cortex as the full-length molecule with a molecular mass of 56 kDa. The association of the presenilins with detergent-insoluble, low-density membrane microdomains, following the isolation of these structures from cerebral cortex by solubilization in Triton X-100 and subsequent sucrose density gradient centrifugation, was also examined. A minor fraction (10%) of both the N- and C-terminal fragments of presenilin-1 was associated with the detergent-insoluble, low-density membrane microdomains, whereas a considerably larger proportion of full-length presenilin-2 was present in the same membrane microdomains. In addition, a significant proportion of full-length presenilin-2 was present in a high-density, detergent-insoluble cytoskeletal pellet enriched in beta-actin. The presence of the presenilins in detergent-insoluble, low-density membrane microdomains indicates a possible role for these specialized regions of the membrane in the lateral separation of Alzheimer's disease-associated proteins within the lipid bilayer and/or in the distinct functions of these proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Compartmentation / physiology
  • Cerebral Cortex / chemistry*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Cytoskeleton / metabolism
  • Detergents
  • Glioma
  • Humans
  • Membrane Proteins / analysis*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Neuroblastoma
  • Neurons / chemistry
  • Neurons / metabolism
  • Peptide Fragments / analysis
  • Presenilin-1
  • Presenilin-2
  • Solubility
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / metabolism


  • Actins
  • Detergents
  • Membrane Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Peptide Fragments
  • Presenilin-1
  • Presenilin-2