Abstract Details

Title Belgian Carriers of Rare ABCA7 Mutations Present with Pronounced Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Topic Aging and Dementia

Presentation(s) S15 - Aging and Dementia 1 (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Objective We aim to delineate the clinicopathological phenotype of rare ABCA7 mutation carriers in Belgian cerebral amyloid angiopathy (CAA) patients.

Background ABCA7 is a major risk gene for Alzheimer’s disease (AD) and rare premature termination codon (PTC) and missense mutations are enriched in AD patients. In preliminary studies in a large Belgian cohort of AD patients, we obtained that ABCA7 PTC and missense mutation carriers present with severe levels of CAA at neuropathological examination, as well as a classical AD phenotype.

Design/Methods Genetic screening of ABCA7 in Belgian CAA cohort (n=83), with genotype-phenotype comparison of the ABCA7 carriers using demographic and clinicopathology data.

Results In 20.5% (17/83) of CAA patients a rare ABCA7 mutation was identified. Six patients carried a PTC mutation, 10 a missense mutation and in one patient we found a deletion. Mean age at onset was 66.4±12.8 (range 47-84) years, while mean age at death was 68.0±10.3 (range 48-92) years. In 87.5% (7/8) of patients a positive family history of disease was mentioned. Nine patients were diagnosed as probable CAA, for which in two AD was associated. Four patients were diagnosed as possible CAA. Carriers predominantly presented with typical lobar intracerebral hemorrhages (ICH). Cognitive decline was present in 52.9% (9/17) of patients. In six patients postmortem examination was available, showing moderate-to-severe levels of CAA in all but one patient (83.3%, 5/6) and AD neuropathological hallmarks (100%, 6/6). Extensive levels of CAA were present in both the meningeal and capillary blood vessels, and moderate to high levels of CAA in the parenchymal blood vessels

Conclusions Our data suggests that rare ABCA7 mutations are frequently present in CAA patients. Carriers show signs of severe levels of CAA, as well as AD neuropathological hallmarks. The findings of this study have important implications for future research and clinical practice.

Authors/Disclosures
Elisabeth Hendrickx Van de Craen, MD (ZNA) PRESENTER	Dr. Hendrickx Van de Craen has nothing to disclose.
	No disclosure on file
Anne Sieben, MD (Gent University Hospital)	Dr. Sieben has nothing to disclose.
Sebastiaan Engelborghs, MD, PhD (University of Antwerp, Biomedical Sciences)	No disclosure on file
	No disclosure on file
	No disclosure on file
Peter P. De Deyn, MD, PhD	Dr. De Deyn has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for elsevier.
Patrick Cras, MD, PhD (University of Antwerp)	The institution of Dr. Cras has received research support from Belgian Fund for Scientific Research. Dr. Cras has received personal compensation in the range of $0-$499 for serving as a member with National Bioethics Committee.
Christine Van Broeckhoven, PhD (University of Antwerp - CDE)	Dr. Van Broeckhoven has nothing to disclose.

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