Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses?
BACKGROUND
Tau and beta-amyloid (Abeta) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific pathology, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects.


OBJECTIVE
To correlate antemortem cerebrospinal fluid (CSF) tau and Abeta levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Abeta.


METHODS
Prospective study.


METHODS
Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects.


METHODS
Correlation of CSF tau and Abeta with final diagnosis.


RESULTS
Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Abeta42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL).


CONCLUSIONS
Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean +/- 2 SDs of the cognitively normal cohort.
Clark
Christopher M
CM
Departments of Neurology, Center for Neuerodegenerative Disease Research, alzheimer's Disease Center, Philadelphia, PA 19104, USA. clarkc@mail.med.upenn.edu
Xie
Sharon
S
Chittams
Jesse
J
Ewbank
Douglas
D
Peskind
Elaine
E
Galasko
Douglas
D
Morris
John C
JC
McKeel
Daniel W
DW
Farlow
Martin
M
Weitlauf
Sharon L
SL
Quinn
Joseph
J
Kaye
Jeffrey
J
Knopman
David
D
Arai
Hiroyuki
H
Doody
Rachelle S
RS
DeCarli
Charles
C
Leight
Susan
S
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D019540:Area Under Curve; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D015331:Cohort Studies; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins