Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease.
To better understand amyloid-beta (Abeta) metabolism in vivo, we assessed the concentration of Abeta in the CSF and plasma of APP(V717F) (PDAPP) transgenic mice, a model that develops age-dependent Alzheimer's disease (AD)-like pathology. In 3-month-old mice, prior to the development of Abeta deposition in the brain, there was a highly significant correlation between Abeta levels in CSF and plasma. In 9-month-old-mice, an age at which some but not all mice have developed Abeta deposition, there was also a significant correlation between CSF and plasma Abeta; however, the correlation was not as strong as that present in young mice. In further exploring CSF and plasma Abeta levels in 9-month-old mice, levels of CSF Abeta were found to correlate highly with Abeta burden. Analysis of the CSF: plasma Abeta ratio revealed a selective two-fold increase in plaque versus non-plaque bearing mice, strongly suggesting a plaque-mediated sequestration of soluble Abeta in brain. Interestingly, in 9-month-old mice, a significant correlation between CNS and plasma Abeta was limited to mice lacking Abeta deposition. These findings suggest that there is a dynamic equilibrium between CNS and plasma Abeta, and that plaques create a new equilibrium because soluble CNS Abeta not only enters the plasma but also deposits onto amyloid plaques in the CNS.
DeMattos
Ronald B
RB
Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Bales
Kelly R
KR
Parsadanian
Maia
M
O'Dell
Mark A
MA
Foss
Eric M
EM
Paul
Steven M
SM
Holtzman
David M
DM
D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000097:blood* / Q000134:cerebrospinal fluid*; D000818:Animals; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002946:Cisterna Magna / Q000502:physiology / Q000601:surgery; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006179:Gyrus Cinguli / Q000737:chemistry / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008866:Microsurgery / Q000379:methods; D019635:Neurosurgical Procedures / Q000379:methods; D058225:Plaque, Amyloid / Q000378:metabolism*; D012737:Sex Factors
D016229:Amyloid beta-Peptides