Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231.
BACKGROUND
Phosphorylation of tau protein at threonine 231 (using full-length tau, 441 amino acids, for the numbering scheme) (p-tau(231)) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF).


OBJECTIVE
To determine to what extent CSF levels of p-tau(231) distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-tau(231) levels are a better diagnostic marker than levels of total tau protein (t-tau) in CSF.


METHODS
Cross-sectional, multicenter, memory clinic-based studies.


METHODS
One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls.


METHODS
Levels of CSF tau proteins as measured with enzyme-linked immunosorbent assays.


RESULTS
Mean CSF levels of p-tau(231) were significantly elevated in the AD group compared with all other groups. Levels of p-tau(231) did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-tau(231) levels improved diagnostic accuracy compared with t-tau levels when patients with AD were compared with healthy controls (P =.03) and demented subjects (P<.001), particularly those with FTD (P<.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-tau(231) compared with t-tau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers.


CONCLUSIONS
Increased levels of CSF p-tau(231) may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.
Buerger
Katharina
K
Dementia Research Section and Memory Clinic, Alzheimer Memorial Center, Geriatric Psychiatry Branch, Department of Psychiatry, Ludwig-Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany. katharina.buerger@psy.med.uni-muenchen.de
Zinkowski
Raymond
R
Teipel
Stefan J
SJ
Tapiola
Tero
T
Arai
Hiroyuki
H
Blennow
Kaj
K
Andreasen
Niels
N
Hofmann-Kiefer
Klaus
K
DeBernardis
John
J
Kerkman
Daniel
D
McCulloch
Cheryl
C
Kohnken
Russell
R
Padberg
Frank
F
Pirttilä
Tuula
T
Schapiro
Marc B
MB
Rapoport
Stanley I
SI
Möller
Hans-Jürgen
HJ
Davies
Peter
P
Hampel
Harald
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers; D003430:Cross-Sectional Studies; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010766:Phosphorylation; D012680:Sensitivity and Specificity; D013912:Threonine / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D016875:tau Proteins; D013912:Threonine