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PMID: 10550330 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Elimination of the class A scavenger receptor does not affect amyloid plaque formation or neurodegeneration in transgenic mice expressing human amyloid protein precursors.

The American journal of pathology ·Vol. 155 ·No. 5 ·1999-11-00 ·Pages 1741-7

Huang F, Buttini M, Wyss-Coray T, McConlogue L, Kodama T, Pitas RE, Mucke L

Abstract

The class A scavenger receptor (SR) is expressed on reactive microglia surrounding cerebral amyloid plaques in Alzheimer's disease (AD). Interactions between the SR and amyloid beta peptides (Abeta) in microglial cultures elicit phagocytosis of Abeta aggregates and release of neurotoxins. To assess the role of the SR in amyloid clearance and Abeta-associated neurodegeneration in vivo, we used the platelet-derived growth factor promoter to express human amyloid protein precursors (hAPPs) in neurons of transgenic mice. With increasing age, hAPP mice develop AD-like amyloid plaques. We bred heterozygous hAPP (hAPP(+/-)) mice that were wild type for SR (SR(+/+)) with SR knockout (SR(-/-)) mice. Crosses among the resulting hAPP(+/-)SR(+/-) offspring yielded hAPP(+/-) and hAPP(-/-) littermates that were SR(+/+) or SR(-/-). These second-generation mice were analyzed at 6 and 12 months of age for extent of cerebral amyloid deposition and loss of synaptophysin-immunoreactive presynaptic terminals. hAPP(-/-)SR(-/-) mice showed no lack of SR expression, plaque formation, or synaptic degeneration, indicating that lack of SR expression does not result in significant accumulation of endogenous amyloidogenic or neurotoxic factors. In hAPP(+/-) mice, ablation of SR expression did not alter number, extent, distribution, or age-dependent accumulation of plaques; nor did it affect synaptic degeneration. Our results do not support a critical pathogenic role for microglial SR expression in neurodegenerative alterations associated with cerebral beta amyloidosis.

MeSH Terms
Alzheimer Disease/genetics,pathology,physiopathology Amyloid beta-Peptides/physiology Amyloid beta-Protein Precursor/physiology Animals Gene Expression Regulation/physiology Humans Membrane Proteins Mice Mice, Transgenic Plaque, Amyloid/pathology Receptors, Immunologic/physiology Receptors, Lipoprotein Receptors, Scavenger Scavenger Receptors, Class A Scavenger Receptors, Class B
Chemicals
Amyloid beta-Peptides Amyloid beta-Protein Precursor Membrane Proteins Receptors, Immunologic Receptors, Lipoprotein Receptors, Scavenger Scarb1 protein, mouse Scavenger Receptors, Class A Scavenger Receptors, Class B
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Huang F
Gladstone Institute of Neurological Disease, Department of Neurology, University of California, San Francisco, USA.
Buttini M
Wyss-Coray T
McConlogue L
Kodama T
Pitas R E
Mucke L
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65489-2
Published
1999-11-00
Pages
1741-7
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1866996
Subset
IM
Grants
NIA NIH HHS · R01 AG011385 · United States
NIA NIH HHS · R37 AG011385 · United States
NIA NIH HHS · AG11385 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)65489-2 PMC Full Text View journal details
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