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Page 39
December 06-07 , 2018
Amsterdam, Nether l ands
Journal of Neuropsychiatry
ISSN: 2471-8548 Alzheimer’s and Dementia 2018
1 3 t h W o r l d c o n g r e s s o n
Alzheimer’s and Dementia
Recent genetic studies suggested an important role for rare deleterious premature termination codon (PTC) mutations in
ABCA7 in early-onset Alzheimer’s disease (EOAD). ABCA7 was originally associated with late-onset Alzheimer’s disease
(AD) in genome-wide association studies. These ABCA7 mutations are predicted to lead to a loss of functional protein, though
their exact mode-of-action is still under investigation. The pathogenicity and segregation patterns of specific mutations and
possible modifiers thereof are still poorly understood. We investigated the frequency of ABCA7 PTC mutations in 734 Belgian
EOAD patients (mean onset age 61.2±7.0 years) and the clinicopathological features of the mutation carriers. We identified
13 different ABCA7 PTC mutations in 32 carriers (32/734, 4.36 %). Carriers had a mean onset age of 61.7±5.9 (48-70) years.
Clinical presentation was predominantly amnestic, except for one patient. No clear distinguishing features were present in the
clinical neurological examination or ancillary investigations. A positive first-degree familial history was present in 73.7% (14/19).
Neuropathological examination (n=5) showed hallmark AD lesions in 80% (4/5) combined with a pronounced cerebral amyloid
angiopathy (CAA). In summary, PTC mutations in ABCA7 are relatively frequent in Belgian EOAD patients, particularly in familial
EOAD. Most carriers have a predominant amnestic presentation and their neuropathology shows AD hallmarks in combination
with CAA. Continued identification and characterization of ABCA7 mutations is necessary to allow implementation of ABCA7
screening in clinical practice and genetic counselling. Also, ABCA7 PTC carriers might represent an important genetic subtype of
AD and more knowledge might improve genetic diagnosis, risk prediction and development of targeted therapeutics.
Genetic and clinicopathological contribution
of rare ABCA7 mutations in Belgian early onset
Alzheimer’s disease patients
Liene Bossaerts1,2,3, Tobi Van den Bossche 1,2,4,5, Arne De
Roeck1,2,3, Sebastiaan Engelborghs2,3,4, Karin Peeters1,2,3,
Marleen Van den Broeck1,2,3, Annelies Laureys1,2,3, Peter P De
Deyn2,3,4, Kristel Sleegers1,2,3, Patrick Cras2,5 and Christine Van
Broeckhoven1,2,3
1Center for Molecular Neurology-VIB, University of Antwerp, Belgium
2Institute Born-Bunge-University of Antwerp, Belgium
3University of Antwerp, Belgium
4Hospital Network Antwerp, Belgium
5Antwerp University Hospital, Belgium
J Neurol Neurosci 2018, Volume: 2
DOI: 10.21767/2471-8548-C1-003