Lack of APOE Christchurch variant in five age of onset outliers with PSEN1, PSEN2 Alzheimer's disease and MAPT frontotemporal dementia

[摘要] Introduction: Age of onset modifiers are of considerable importance in Alzheimer's and related dementias. Arboleda-Valesquez et al., reporting on a single PSEN1 subject, suggested that homozygosity for the Christchurch variant of APOE could represent such a modifier. Methods: We studied APOE Christchurch and Kloth-VS genotypes of five dementia age of onset outliers who carried their families' pathogenic variant, but were asymptomatic at ages beyond the families' average age of onset. Results: Four age of onset outliers with PSEN1/2 and MAPT mutations did not carry the Christchurch variant and a fifth individual was also determined to not be homozygous for this variant. Among them, only one subject (APOE epsilon 3/epsilon 3) carries the Klotho-VS heterozygous genotype. Discussion: From a small but informative sample of five age of onset outliers we show that neither the APOE Christchurch nor the Klotho-VS variant is a common age of onset modifier for three genetic forms of dementia. Larger studies of this association and further research is required to identify additional genetic modifiers.

[发布日期] 2020-11-15

[关键词] Dementia;Alzheimer's disease;APOE;Christchurch mutation;Modifiers