APOE ɛ2 is associated with white matter hyperintensity volume in CADASIL.
Apolipoprotein E (APOE) increases the risk for Alzheimer’s disease (ɛ4 allele) and cerebral amyloid angiopathy (ɛ2 and ɛ4), but its role in small vessel disease (SVD) is debated. Here we studied the effects of APOE on white matter hyperintensity volume (WMHV) in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a nonamyloidogenic angiopathy and inherited early-onset form of pure SVD. Four hundred and eighty-eight subjects were recruited through a multicenter consortium. Compared with APOE ɛ3/ɛ3, WMHV was increased in APOE ɛ2 (P = 0.02) but not APOE ɛ4. The results remained significant when controlled for genome-wide genetic background variation. Our findings suggest a modifying influence of APOE ɛ2 on WMHV caused by pure SVD.
Benno
B
Gesierich
Christian
C
Opherk
Jonathan
J
Rosand
Mariya
M
Gonik
Rainer
R
Malik
Eric
E
Jouvent
Dominique
D
Hervé
Poneh
P
Adib-Samii
Steve
S
Bevan
Luigi
L
Pianese
Serena
S
Silvestri
Maria T
MT
Dotti
Nicola
N
De Stefano
Jeroen
J
van der Grond
Elles M J
EM
Boon
Francesca
F
Pescini
Natalia
N
Rost
Leonardo
L
Pantoni
Saskia A Lesnik
SA
Oberstein
Antonio
A
Federico
Michele
M
Ragno
Hugh S
HS
Markus
Elisabeth
E
Tournier-Lasserve
Hugues
H
Chabriat
Martin
M
Dichgans
Marco
M
Duering
Michael
M
Ewers
D000328:Adult; D000483:Alleles; D053329:Apolipoprotein E2 / Q000235:genetics / Q000378:metabolism*; D046589:CADASIL / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms; D012044:Regression Analysis; D012307:Risk Factors; D066127:White Matter / Q000473:pathology*
D053329:Apolipoprotein E2; D020033:Protein Isoforms