Neuronal cell death in Alzheimer's disease correlates with apoE uptake and intracellular Aβ stabilization

Frank M. LaFerla, Juan C Troncoso, Dudley K. Strickland, Claudia H. Kawas, Gilbert Jay

Research output: Contribution to journalArticle

Abstract

The brains of individuals with Alzheimer's disease (AD) are characterized by extracellular deposition of β-amyloid protein (Aβ), intracellular neurofibrillary tangles, and loss of neurons. To study molecular markers associated with dying cells in the AD brain, in situ DNA labeling techniques were used to visualize cells with DNA fragmentation. We observed that intracellular accumulation of apolipoprotein E (apoE) is correlated with the detection of intracellular Aβ-like immunoreactivity within the same cytoplasmic granules, suggesting that uptake of lipids may have stabilized the hydrophobic Aβ protein within the cell. These apoE- containing neurons also exhibit high expression of a cell surface receptor, gp330, which is known to bind apoE. Cells containing significant nuclear DNA fragmentation express the highest level of cell surface gp330. Extracellular deposition of Aβ is detected only upon neuronal cell death, initially as halos of Aβ immunoreactivity around individual dying neurons, and subsequently as Aβ plaques containing numerous neuronal cell ghosts. Based on our in situ analysis of nuclear DNA fragmentation, we conclude that neuronal cell death likely occurs before the extracellular deposition of Aβ in AD brains.

Original languageEnglish (US)
Pages (from-to)310-320
Number of pages11
JournalJournal of Clinical Investigation
Volume100
Issue number2
StatePublished - Jul 15 1997

Fingerprint

Apolipoproteins E
Alzheimer Disease
Cell Death
DNA Fragmentation
Neurons
Brain
Cytoplasmic Granules
Serum Amyloid A Protein
Neurofibrillary Tangles
Cell Surface Receptors
Lipids
DNA
Proteins

Keywords

  • β-amyloid protein
  • Alzheimer's disease
  • Apolipoprotein E
  • Apoptotic cell death
  • Glycoprotein 330

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Neuronal cell death in Alzheimer's disease correlates with apoE uptake and intracellular Aβ stabilization. / LaFerla, Frank M.; Troncoso, Juan C; Strickland, Dudley K.; Kawas, Claudia H.; Jay, Gilbert.

In: Journal of Clinical Investigation, Vol. 100, No. 2, 15.07.1997, p. 310-320.

Research output: Contribution to journalArticle

LaFerla, Frank M. ; Troncoso, Juan C ; Strickland, Dudley K. ; Kawas, Claudia H. ; Jay, Gilbert. / Neuronal cell death in Alzheimer's disease correlates with apoE uptake and intracellular Aβ stabilization. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 2. pp. 310-320.
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