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Abstract Details

Genotype-Phenotype Data of Rare ABCA7 Missense Mutations in Belgian Alzheimer’s Disease Patients
Aging, Dementia, and Behavioral Neurology
Aging and Dementia Posters (7:00 AM-5:00 PM)
006
To delineate the clinicopathological Alzheimer’s disease (AD) phenotype of ABCA7 missense mutation carriers, and to compare genotype–phenotype data with AD patients carrying an ABCA7 premature termination codon (PTC) variant. ABCA7 was associated to risk for Alzheimer’s disease (AD) in GWAS, and rare PTC variants and missense variants are enriched in AD patients.
Using targeted resequencing of the ABCA7 coding region in a large Belgian AD cohort (n=1365), we identified 100 missense carriers and 68 PTC carriers.
Available demographic and clinicopathological data of missense and PTC mutation carriers were reviewed.
Mean onset age of ABCA7 missense carriers was 68.0±9.9 years (37-92), with mean disease duration of 9.6±4.4 years. Positive first-degree familial history was present in 62.5%, and apparent autosomal dominant co-segregation of AD was observed in a family (p.G1820S). Probable AD was mainly diagnosed, but in 16% we observed important vascular involvement. Clinical neurological examination and neuroimaging showed typical signs of AD. Cerebrospinal fluid (CSF) AD biomarkers were available in 37 missense carriers, showing a typical AD profile in 80%. Additionally, (re)analysis of CSF biomarkers is ongoing in 55 carriers. Brain autopsy (n=7) revealed classical AD changes together with moderate-to-high levels of cerebral amyloid angiopathy (CAA) and capillary CAA in all. ABCA7 PTC carriers had a similar onset age (69.5 years) as missense carriers (68.0 years), although both presented with a wide onset range. Besides higher total tau levels in PTC carriers, there were no significant differences in CSF AD-biomarker levels seen. Extensive levels of CAA were present in both missense (n=7) and PTC carriers (n=10), as well as capillary CAA.
ABCA7 missense mutation carriers present with a classical AD phenotype. Remarkably, additional to AD neuropathological hallmarks, extensive levels of CAA were present in both missense and PTC carriers. These findings 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
Bernard J. Hanseeuw, MD, PhD (Massachusetts General Hospital) Dr. Hanseeuw has nothing to disclose.
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.