Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes

Jane F. Diedrich, Hal Minnigan, Richard I. Carp, John N. Whitaker, Richard Race, William Frey, Ashley T. Haase

Research output: Contribution to journalArticle

279 Citations (Scopus)

Abstract

With the rationale that the neuropathological similarities between scrapie and Alzheimer's disease reflect convergent pathological mechanisms involving altered gene expression, we set out to identify molecular events involved in both processes, using scrapie as a model to study the time course of these changes. We differentially screened a cDNA library constructed from scrapie-infected mice to identify mRNAs that increase or decrease during disease and discovered in this way two mRNAs that are increased in scrapie and Alzheimer's disease. These mRNAs were subsequently shown by sequence analysis to encode apolipoprotein E and cathepsin D (EC 3.4.23.5). Using in situ hybridization and immunocytochemistry to define the cellular and anatomic pathology of altered gene expression, we found that in both diseases the increase in apolipoprotein E and cathepsin D mRNAs and proteins occurred in activated astrocytes. In scrapie, the increase in gene expression occurred soon after the amyloid-forming abnormal isoform of the prion protein has been shown to accumulate in astrocytes. In Alzheimer's disease, the increased expression of cathepsin D also occurred in association with β-amyloid. These studies reveal some of the molecular antecedents of neuropathological changes in scrapie and Alzheimer's disease and accord new prominence to the role of astrocytes in neurodegenerative conditions.

Original languageEnglish (US)
Pages (from-to)4759-4768
Number of pages10
JournalJournal of Virology
Volume65
Issue number9
StatePublished - Sep 1991
Externally publishedYes

Fingerprint

Apolipoproteins D
cathepsin D
Scrapie
apolipoprotein E
Cathepsin D
scrapie
astrocytes
Apolipoproteins E
Alzheimer disease
Astrocytes
Alzheimer Disease
Messenger RNA
amyloid
Gene Expression
Amyloid
gene expression
prions
immunocytochemistry
Gene Library
cDNA libraries

ASJC Scopus subject areas

  • Immunology

Cite this

Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes. / Diedrich, Jane F.; Minnigan, Hal; Carp, Richard I.; Whitaker, John N.; Race, Richard; Frey, William; Haase, Ashley T.

In: Journal of Virology, Vol. 65, No. 9, 09.1991, p. 4759-4768.

Research output: Contribution to journalArticle

Diedrich, Jane F. ; Minnigan, Hal ; Carp, Richard I. ; Whitaker, John N. ; Race, Richard ; Frey, William ; Haase, Ashley T. / Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes. In: Journal of Virology. 1991 ; Vol. 65, No. 9. pp. 4759-4768.
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