APOE ɛ2 is associated with white matter hyperintensity volume in CADASIL.

Abstract

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.

• Authors: Benno Gesierich, Christian Opherk, Jonathan Rosand, Mariya Gonik, Rainer Malik, Eric Jouvent, Dominique Hervé, Poneh Adib-Samii, Steve Bevan, Luigi Pianese, Serena Silvestri, Maria T Dotti, Nicola De Stefano, Jeroen van der Grond, Elles M J Boon, Francesca Pescini, Natalia Rost, Leonardo Pantoni, Saskia A Lesnik Oberstein, Antonio Federico, Michele Ragno, Hugh S Markus, Elisabeth Tournier-Lasserve, Hugues Chabriat, Martin Dichgans, Marco Duering, Michael Ewers
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 36 Issue 1 Pg. 199-203 (Jan 2016) ISSN: 1559-7016 [Electronic] United States
• PMID: 25920955 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein E2
• Protein Isoforms

Topics

• Adult
• Alleles
• Apolipoprotein E2 (genetics, metabolism)
• CADASIL (genetics, metabolism, pathology)
• Female
• Gene Frequency (genetics)
• Genome-Wide Association Study
• Genotype
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Protein Isoforms
• Regression Analysis
• Risk Factors
• White Matter (pathology)