TOMM40-APOE haplotypes are associated with cognitive decline in non-demented Blacks.


Deters KD(1), Mormino EC(1), Yu L(2), Lutz MW(3), Bennett DA(2), Barnes LL(2).
Author information:
(1)Stanford University School of Medicine, Department of Neurology and Neurological Sciences, Stanford, California, USA.
(2)Rush University Medical Center, Department of Neurological Sciences, Rush Alzheimer's Disease Center, Chicago, Illinois, USA.
(3)Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA.


INTRODUCTION: The goal was to investigate effects of APOE-TOMM40-'523 haplotypes on cognitive decline in non-demented non-Hispanic Blacks (NHB), and determine whether effects differ from non-Hispanic Whites (NHW). METHODS: The impact of zero to two copies of the '523-Short variant (S; poly-T alleles < 20) within apolipoprotein E (APOE) genotype on a composite measure of global cognition and five domains was examined. RESULTS: In NHB with ε3/ε3 (N = 294), '523-S/S was associated with faster decline in global cognition (β = -0.048, P = 0.017), episodic memory (β = -0.05, P = 0.031), and visuospatial ability (β = -0.037, P = 0.034) relative to those without '523-S. For NHB ε4+ (N = 182), '523-S/S had slower decline in global cognition (β = 0.047, P = 0.042) and visuospatial ability (β = 0.07, P = 0.0005) relative to '523-S non-carriers. NHB ε4+ with '523-S also had a slower rate of decline than NHWs ε4+ with '523-S. DISCUSSION: '523-S/S has a different effect on cognitive decline among NHB dependent on APOE allele. Differences in the effect of ε4-'523-S in NHB may explain prior mixed findings on ε4 and decline in this population.