Intra-individual stability of CSF biomarkers for Alzheimer's disease over two years.
This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau(181) (P-tau(181)) and amyloid-beta(1-42) (Abeta(1-42)). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau(181) levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group (p<0.01), while baseline Abeta(1-42) levels were lower (p<0.001). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 (p<0.001) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.
Zetterberg
Henrik
H
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden. henrik.zetterberg@clinchem.gu.se
Pedersen
Mona
M
Lind
Karin
K
Svensson
Maria
M
Rolstad
Sindre
S
Eckerström
Carl
C
Syversen
Steinar
S
Mattsson
Ulla-Britt
UB
Ysander
Christina
C
Mattsson
Niklas
N
Nordlund
Arto
A
Vanderstichele
Hugo
H
Vanmechelen
Eugeen
E
Jonsson
Michael
M
Edman
Ake
A
Blennow
Kaj
K
Wallin
Anders
A
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins