CSF biomarkers in relationship to cognitive profiles in Alzheimer disease.
OBJECTIVE
To investigate the relationship between CSF biomarkers and cognitive profiles in Alzheimer disease (AD).


METHODS
We included 177 patients with AD. Digit Span, Visual Association Test (VAT), VAT object naming, Trail Making Test (TMT), and category fluency were used to assess cognitive functions. Disease severity was assessed using Mini-Mental State Examination; functional impairment was rated by Clinical Dementia Rating. In CSF, levels of amyloid-beta 1-42 (Abeta(1-42)), tau, and tau phosphorylated at threonine 181 (p-tau) were measured. K-means cluster analysis was performed with the three biomarkers to obtain three clusters. Multivariate analysis of variance for repeated measures was performed with CSF cluster as between-subjects factor, neuropsychological z scores as within-subjects variable, and age, sex, and education as covariates.


RESULTS
Cluster 1 consisted of 88 patients (49%) with relatively high levels of Abeta(1-42) and low levels of tau and p-tau. Cluster 2 contained 72 patients (41%) with relatively low levels of Abeta(1-42) and high levels of tau and p-tau. Cluster 3 was made up of 17 patients (10%) with low levels of Abeta(1-42) and very high levels of tau and p-tau. No differences between clusters on age, sex, education, APOE genotype, disease duration, functional impairment, or disease severity were found. Patients in cluster 3 performed worse on VAT, TMT-A and -B, and fluency.


CONCLUSIONS
Clusters of CSF biomarker levels are related to cognitive profiles in Alzheimer disease. A subgroup of patients with extremely high CSF levels of tau and tau phosphorylated at threonine 181 shows a distinct cognitive profile with more severe impairment of memory, mental speed, and executive functions, which cannot be explained by disease severity.
van der Vlies
A E
AE
Department of Neurology and Alzheimer Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. ae.vdvlies@vumc.nl
Verwey
N A
NA
Bouwman
F H
FH
Blankenstein
M A
MA
Klein
M
M
Scheltens
P
P
van der Flier
W M
WM
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology*; D000595:Amino Acid Sequence / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000523:psychology; D008606:Mental Processes / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000032:analysis / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D012720:Severity of Illness Index; D013912:Threonine / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D013912:Threonine