Association of elevated phospho-tau levels with Alzheimer-typical 18F-fluoro-2-deoxy-D-glucose positron emission tomography findings in patients with mild cognitive impairment.
BACKGROUND
Mild cognitive impairment is considered to be a transitional stage between normal aging and dementia. Phosphorylated tau protein in cerebrospinal fluid and even more decrements of cerebral glucose metabolism in parietal, temporal, or cingulate regions have shown favorable specificity for the diagnosis of Alzheimer dementia and could be useful supplementary tools to determine Alzheimer pathology in early stages.


METHODS
We measured cerebrospinal fluid tau phosphorylated at threonine 181 protein, cerebrospinal fluid total tau, and cerebral glucose metabolism using 18F-fluoro-2-deoxy-D-glucose positron emission tomography in 16 patients with mild cognitive impairment and age-matched control subjects.


RESULTS
Alzheimer-typical patterns of cerebral glucose metabolism were significantly related to elevated phosphorylated tau levels (p =.009) but not to elevated total tau levels. In six of seven mild cognitive impairment patients with increased phosphorylated tau concentrations, Alzheimer disease-typical positron emission tomography patterns were found. Phosphorylated tau measurement separated patients with and without Alzheimer disease-typical positron emission tomography findings with a sensitivity of 85.7% and a specificity of 88.9%.


CONCLUSIONS
Unlike total tau levels, elevated phosphorylated tau levels were strictly related to Alzheimer-typical patterns of cerebral glucose metabolism in mild cognitive impairment patients. The results can be interpreted as validation of phosphorylated tau measurements for detecting Alzheimer disease in mild cognitive impairment patients.
Department of Psychiatry, University of Mainz, Mainz, Germany. fellgiebel@psychiatrie.klinik.uni-mainz.de
Andreas
A
Fellgiebel
Thomas
T
Siessmeier
Armin
A
Scheurich
Georg
G
Winterer
Peter
P
Bartenstein
Lutz G
LG
Schmidt
Matthias J
MJ
Müller
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D001923:Brain Chemistry; D001931:Brain Mapping; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010766:Phosphorylation; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric; D014055:Tomography, Emission-Computed / Q000379:methods; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose