Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: a risk for AD?
BACKGROUND
Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood.


METHODS
The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4 allele, and 20 had the APOE epsilon34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance.


RESULTS
The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of epsilon4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe.


CONCLUSIONS
Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.
Persson
J
J
Department of Psychology, Umeå University, S-901 87 Umeå, Sweden. perssonj@umich.edu
Lind
J
J
Larsson
A
A
Ingvar
M
M
Cruts
M
M
Van Broeckhoven
C
C
Adolfsson
R
R
Nilsson
L-G
LG
Nyberg
L
L
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D002353:Carrier State; D003071:Cognition / Q000502:physiology*; D003704:Dementia / Q000235:genetics; D006580:Genetic Carrier Screening; D006304:Health Status; D006720:Homozygote; D006801:Humans; D008568:Memory; D008875:Middle Aged; D012016:Reference Values; D012307:Risk Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E