Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype.
OBJECTIVE
Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression.


METHODS
Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years.


RESULTS
The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD.


CONCLUSIONS
CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.
Section of Molecular Geriatrics, Department of Public Health, Uppsala University, Uppsala, Sweden.
Elin S
ES
Blom
Vilmantas
V
Giedraitis
Henrik
H
Zetterberg
Hiroaki
H
Fukumoto
Kaj
K
Blennow
Bradley T
BT
Hyman
Michael C
MC
Irizarry
Lars-Olof
LO
Wahlund
Lars
L
Lannfelt
Martin
M
Ingelsson
D000368:Aged; D000544:Alzheimer Disease / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000235:genetics; D053327:Apolipoprotein E4 / Q000134:cerebrospinal fluid* / Q000235:genetics*; D015415:Biomarkers; D003072:Cognition Disorders / Q000523:psychology*; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000235:genetics; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins