Progression from MCI to AD: predictive value of CSF Aβ42 is modified by APOE genotype.
OBJECTIVE
To study CSF biomarkers amyloid-beta 1-42 (Aβ42) and total tau (tau) in relation to APOE genotype in their ability to predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).


METHODS
In 100 MCI patients CSF Aβ42, tau and APOE genotype were determined. At follow-up of 18 (13-24) months 58 patients remained non-progressive and 42 progressed to AD.


RESULTS
Cox proportional hazards models showed an interaction between Aβ42 and APOE genotype (p<0.05). Stratification for APOE revealed HR (95% CI) for abnormal Aβ42 of 8.2 (2.1-31.9) for ε4 non-carriers, 3.9 (0.8-18.5) for heterozygotes and 0.3 (0.0-1.7) for homozygotes. Inversely, stratification for Aβ42 revealed that in patients with normal levels of Aβ42, ε4 homozygotes had a strongly increased risk of progression to AD with HR (95% CI) 20.8 (2.4-182.8). Tau and APOE independently predicted progression to AD.


CONCLUSIONS
Aβ42 was a stronger predictor of progression to AD in APOE ε4 non-carriers than in carriers. Furthermore, the risk of progression for ε4 homozygotes was very high, also in patients with normal levels of Aβ42.
Kester
Maartje I
MI
Alzheimer Center and Department of Neurology, VU University Medical Center Amsterdam, The Netherlands. m.kester@vumc.nl
Verwey
Nicolaas A
NA
van Elk
Evert J
EJ
Blankenstein
Marinus A
MA
Scheltens
Philip
P
van der Flier
Wiesje M
WM
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000235:genetics*; D011237:Predictive Value of Tests; D012720:Severity of Illness Index
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)