Abeta levels in serum, CSF and brain, and cognitive deficits in APP + PS1 transgenic mice.
We compared beta-amyloid peptide (Abeta) levels in the serum, CSF and brain (hippocampus) and correlated these with spatial learning in APP+PS1 transgenic mice. Compared with non-transgenic littermates, male 14-month-old APP + PS1 mice were impaired in spatial learning in the water maze. Among the APP + PS1 mice, only the hippocampal insoluble Abeta42 level correlated with spatial memory (r = -0.44). The levels of insoluble Abeta40 and Abeta42 were highly correlated (r = 0.92), and also correlated with soluble hippocampal Abeta42 (r = 0.64/0.69), which further correlated with the CSF Abeta42 (r = 0.52). None of these parameters correlated with serum Abeta40 levels. These findings support the role of insoluble Abeta42 in memory dysfunction and suggest a model with several pools (insoluble, extracellular soluble, CSF) of Abeta being in partial equilibrium with each other.
Liu
Li
L
Department of Neuroscience, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland.
Tapiola
Tero
T
Herukka
Sanna-Kaisa
SK
Heikkilä
Matti
M
Tanila
Heikki
H
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry* / Q000503:physiopathology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D053764:Presenilin-1; D011930:Reaction Time; D012995:Solubility
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)