Increase in beta-amyloid levels in cerebrospinal fluid of children with Down syndrome.
BACKGROUND
Individuals with Down syndrome (DS) invariably develop Alzheimer's disease (AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis.


OBJECTIVE
To investigate how levels of different amyloid-beta (Abeta) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change over time. The first CSF sample was taken at 8 months and the following two samples at 20-40 and 54 months of age.


RESULTS
Individual levels of the Abeta peptides, as well as total Abeta levels in CSF increased over time when measured with Western blot. Tau in CSF decreased whereas there was no change in levels of phosphorylated tau over time.


CONCLUSIONS
The increasing levels of Abeta in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the Abeta precursor APP, which leads to an overproduction of Abeta. Despite the increased CSF concentrations of Abeta, there were no signs of an AD-indicating tau pattern in CSF, since the levels of total tau decreased and phosphorylated tau remained unchanged. This observation further strengthens the theory of Abeta pathology preceding tau pathology in AD.
Englund
Hillevi
H
Department of Public Health and Caring Sciences, Section of Molecular Geriatrics, Uppsala University, and Department of Women's and Children's Health, Uppsala University Children's Hospital, Sweden.
Annerén
Göran
G
Gustafsson
Jan
J
Wester
Ulrika
U
Wiltfang
Jens
J
Lannfelt
Lars
L
Blennow
Kaj
K
Höglund
Kina
K
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D002675:Child, Preschool; D004314:Down Syndrome / Q000134:cerebrospinal fluid* / Q000150:complications; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016875:tau Proteins