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.
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden. henrik.zetterberg@clinchem.gu.se
Henrik
H
Zetterberg
Mona
M
Pedersen
Karin
K
Lind
Maria
M
Svensson
Sindre
S
Rolstad
Carl
C
Eckerström
Steinar
S
Syversen
Ulla-Britt
UB
Mattsson
Christina
C
Ysander
Niklas
N
Mattsson
Arto
A
Nordlund
Hugo
H
Vanderstichele
Eugeen
E
Vanmechelen
Michael
M
Jonsson
Ake
A
Edman
Kaj
K
Blennow
Anders
A
Wallin
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