Spherons and Alzheimer's disease: Biochemical, immunological and cell biological studies

Paul Averback, Judith Fitzpatrick, Leslie Iversen, Darrell S Kaufman, David Morse

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Senile amyloid plaques (SP), one of the key pathogenetic phenomena and therapeutic targets in Alzheimer's Disease (AD), contain masses of amyloid βprotein (Aβ) of unknown origin. Spherons are regular large Aβ-domain containing intraneuronal protein masses, in the normal gray matter. We investigated biochemical, cell biological, and immunological aspects of the link between spherons and SP. Spherons were extracted from samples of human brain obtained at autopsy and studied for amyloid content by immunolabelling and by Western blots from electrophoretic gels. The transformation of intact spherons to fibrillized β-pleated sheet deposits was studied by transmission electron microscopy and Fourier transform infrared spectroscopy. The degree of spheron protein racemization was measured by reverse phase high performance liquid chromatography. Spherons were found to be immunopositive for Aβ and APR and to demonstrate fibrillogenesis similar to SP. Enantiomeric analysis showed spheron chiral content closely similar to SP, with spheron protein on average 20-40 years old, consistent with gradual protein accumulation over the lifetime of the individual. These findings suggest that the highly racemized fibrillogenic spheron is an intracellularly sequestered long-lived insoluble stable source of intact Aβ domain, and support the possible link between spherons and SP.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalAlzheimer's Reports
Volume3
Issue number3
StatePublished - 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Averback, P., Fitzpatrick, J., Iversen, L., Kaufman, D. S., & Morse, D. (2000). Spherons and Alzheimer's disease: Biochemical, immunological and cell biological studies. Alzheimer's Reports, 3(3), 177-184.