Reduction of phosphorylated tau during memantine treatment of Alzheimer's disease.
BACKGROUND
Memantine is a moderate affinity N-methyl-D-aspartate receptor antagonist approved for treatment of Alzheimer's disease (AD). In AD, tau is abnormally hyperphosphorylated. However, no significant changes of phosphorylated tau levels in CSF are found at follow-up in studies with AD patients. It has been shown in vitro that memantine reverse induced abnormal hyperphosphorylation of tau in hippocampal neurons of rats.


METHODS
Eleven AD patients were examined with cognitive tests and interviews of relatives. CSF analyses were performed before starting treatment with memantine as well as after 1 year.


RESULTS
A statistically significant reduction of CSF phosphorylated tau at the 1-year follow-up was seen, from median 126 (interquartile range 107-153) to 108 (88-133) ng/l (p = 0.018). No statistically significant differences of total tau or Abeta42 were found.


CONCLUSIONS
The results may reflect effects of memantine on a key pathological feature in AD in line with previous in vitro findings.
Degerman Gunnarsson
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M
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University Hospital, Uppsala, Sweden. degerman.gunnarsson@akademiska.se
Kilander
L
L
Basun
H
H
Lannfelt
L
L
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D018691:Excitatory Amino Acid Antagonists; D016875:tau Proteins; D008559:Memantine