doi: 10.1212/WNL.0000000000002628. Epub 2016 Apr 1.
Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation
Tobi Van den Bossche 1, Kristel Sleegers 1, Elise Cuyvers 1, Sebastiaan Engelborghs 1, Anne Sieben 1, Arne De Roeck 1, Caroline Van Cauwenberghe 1, Steven Vermeulen 1, Marleen Van den Broeck 1, Annelies Laureys 1, Karin Peeters 1, Maria Mattheijssens 1, Mathieu Vandenbulcke 1, Rik Vandenberghe 1, Jean-Jacques Martin 1, Peter P De Deyn 1, Patrick Cras 1, Christine Van Broeckhoven; Belgian Neurology Consortium
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- PMID:27037232
- PMCID: PMC4917260
- DOI: 10.1212/WNL.0000000000002628
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Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation
Tobi Van den Bossche et al. Neurology..
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Abstract
Objective: To generate a clinical and pathologic phenotype of patients carrying rare loss-of-function mutations in ABCA7, identified in a Belgian Alzheimer patient cohort and in an autosomal dominant family.
Methods: We performed a retrospective review of available data records, medical records, results of CSF analyses and neuroimaging studies, and neuropathology data.
Results: The mean onset age of the mutation carriers (n = 22) was 73.4 ± 8.4 years with a wide age range of 36 (54-90) years, which was independent of APOE genotype and cerebrovascular disease. The mean disease duration was 5.7 ± 3.0 years (range 2-12 years). A positive family history was recorded for 10 carriers (45.5%). All patient carriers except one presented with memory complaints. The 4 autopsied brains showed typical immunohistochemical changes of late-onset Alzheimer disease.
Conclusions: All patients carrying a loss-of-function mutation in ABCA7 exhibited a classical Alzheimer disease phenotype, though with a striking wide onset age range, suggesting the influence of unknown modifying factors.
© 2016 American Academy of Neurology.
Figures
The 4G8 staining shows extensive amyloid angiopathy in 3 out of 4 patients (A) and extensive amyloid senile plaques (B) in the frontal cortex. Classic neurofibrillary tangles are present in the hippocampal CA1 (C [AT8 stain]). In photographs (D) through (F), the superficial cortical layers of the entorhinal cortex are shown. Multiple neuronal intracytoplasmic inclusions stain with p62 (D), AT8 (E), and TDP-43 (F).
Dark filled symbols indicate patients with AD, the half-filled symbol indicates mild cognitive impairment (MCI), and the quarter-filled symbol indicates subjective cognitive impairment (SCI). The arrow indicates the proband of family DR170. The 5 individuals for whom we have DNA available are marked by an asterisk. The open circle indicates a patient with Parkinson disease (PD). AAO = age at onset in years.
Comment in
- Rare ABCA7 variants in Alzheimer disease: Guilt by association.Swerdlow RH.Swerdlow RH.Neurology. 2016 Jun 7;86(23):2118-9. doi: 10.1212/WNL.0000000000002630. Epub 2016 Apr 1.Neurology. 2016.PMID:27037231No abstract available.
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