Longitudinal observation on CSF Abeta42 levels in young to middle-aged amyloid precursor protein/presenilin-1 doubly transgenic mice.
To relate levels of beta-amyloid42 (Abeta42) in the cerebrospinal fluid (CSF) and brain in early Alzheimer's disease, we repeatedly measured CSF Abeta42 levels in transgenic mice carrying Swedish amyloid precursor protein and presenilin-1 mutations, at ages before and after amyloid deposition. Hippocampal Abeta42 levels were measured at the endpoints. In APPswe/PS1(A246E) mice, CSF Abeta42 levels significantly increased between 5 and 7 months of age but did not change between 8 and 13 months despite a rapid increase in brain Abeta42. Furthermore, a decline in CSF Abeta42 levels was observed between 6 and 9 months in APPswe/PS1dE9 mice with faster pathology. Interestingly, the initial CSF Abeta42 concentrations correlated more strongly with brain Abeta42 levels than the endpoint CSF Abeta42. Our results suggest that the levels of CSF Abeta42 initially reflect the rate of Abeta42 production, but after reaching a critical concentration stay in equilibrium, until plaque formation leads to decreased CSF Abeta42 levels.
Liu
Li
L
Department of Neuroscience and Neurology, University of Kuopio, Finland.
Herukka
Sanna-Kaisa
SK
Minkeviciene
Rimante
R
van Groen
Thomas
T
Tanila
Heikki
H
D000375:Aging; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000473:pathology*; D003115:Colony-Stimulating Factors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments; D053764:Presenilin-1; D013997:Time Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003115:Colony-Stimulating Factors; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1