Increasing CSF phospho-tau levels during cognitive decline and progression to dementia.
BACKGROUND
Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression.


OBJECTIVE
To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline.


METHODS
Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM).


RESULTS
There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up.


CONCLUSIONS
Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
Andersson
Christin
C
Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, NOVUM Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. christin.andersson@ki.se
Blennow
Kaj
K
Almkvist
Ove
O
Andreasen
Niels
N
Engfeldt
Peter
P
Johansson
Sven-Erik
SE
Lindau
Maria
M
Eriksdotter-Jönhagen
Maria
M
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000503:physiopathology; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D010766:Phosphorylation; D015854:Up-Regulation / Q000502:physiology; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; C054369:MAPT protein, human; D016875:tau Proteins