Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model.
The epsilon4 allele of apolipoprotein E (ApoE) is an important genetic risk factor for Alzheimer's disease (AD). Increasing evidence suggests that this association may be linked to the ability of ApoE to interact with the amyloid-beta (Abeta) peptide and influence its concentration and structure. To determine the effect of ApoE on Abeta and other AD pathology in vivo, we used APPsw transgenic mice and ApoE knockout (-/-) mice to generate APPsw animals that carried two (ApoE +/+), one (ApoE +/-), or no copies (ApoE -/-) of the normal mouse ApoE gene. At 12 months of age, Abeta deposition was present in the cortex and hippocampus and was also prominent within leptomeningeal and cortical blood vessels of all APPsw ApoE +/+ mice. Importantly, although Abeta deposition still occurred in APPsw ApoE -/- mice, no fibrillar Abeta deposits were detected in the brain parenchyma or cerebrovasculature. There was also no neuritic degeneration associated with Abeta deposition in the absence of ApoE. These data demonstrate that ApoE facilitates the formation of both neuritic and cerebrovascular plaques, which are pathological hallmarks of AD and cerebral amyloid angiopathy.
Holtzman
D M
DM
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Fagan
A M
AM
Mackey
B
B
Tenkova
T
T
Sartorius
L
L
Paul
S M
SM
Bales
K
K
Ashe
K H
KH
Irizarry
M C
MC
Hyman
B T
BT
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001808:Blood Vessels / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002560:Cerebrovascular Circulation; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016501:Neurites / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E