Association of total tau and phosphorylated tau 181 protein levels in cerebrospinal fluid with cerebral atrophy in mild cognitive impairment and Alzheimer disease.
BACKGROUND
We sought to examine the association of levels of total tau (t-tau) and phosphorylated tau 181 (p-tau181) protein with brain morphology in mild cognitive impairment, as defined by the concept of aging-associated cognitive decline (AACD) and Alzheimer disease.


METHODS
Twenty-three participants with AACD, 16 with Alzheimer disease and 15 healthy controls underwent magnetic resonance imaging and lumbar puncture. We performed voxel-based morphometry to investigate the association between tau levels in cerebrospinal fluid (CSF) and cerebral grey matter density throughout the entire brain.


RESULTS
Voxel-based morphometry revealed that both elevated t-tau and p-tau181 concentrations were associated with reduced grey matter density in temporal, parietal and frontal regions. Among participants with AACD, elevated levels of p-tau181 (but not t-tau) in CSF were correlated with a pronounced atrophy in the right hippocampus.


CONCLUSIONS
Our study was limited by the small sample, especially with respect to the analysis comprising the AACD subgroups. Moreover, we did not correct our voxel-based morphometry analyses for multiple dependent comparisons, therefore they harbour a risk of false-positive results.


CONCLUSIONS
Elevated levels of t-tau and p-tau181 in CSF reflect degenerative processes in the cortical regions typically affected in Alzheimer disease. Our findings in participants with AACD support the hypothesis that p-tau181 might be more specifically related to neurodegenerative changes in early Alzheimer disease.
Thomann
Philipp A
PA
Section of Geriatric Psychiatry, University of Heidelberg, Heidelberg, Germany. philipp_thomann@med.uni-heidelberg.de
Kaiser
Elmar
E
Schönknecht
Peter
P
Pantel
Johannes
J
Essig
Marco
M
Schröder
Johannes
J
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016875:tau Proteins