CADASIL: how to avoid the unavoidable?

All three siblings (one female/two males) of a family presented successively with cerebrovascular events at the ages of 55, 63 and 65. The first one manifested extensive left subcortical haemorrhage and both the second and third patient, showed left lacunar ischemic stroke. Their mother had died from vascular dementia at the age of 60 after several subcortical ischaemic strokes. Their maternal grandfather had died in his fifties from haemorrhagic stroke. All of them showed extensive white matter involvement. The genetic study revealed a mutation in exon 11 of the Notch3 gene in two family members. They were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Although CADASIL is a well-established disease, little is known about this disorder. The fact that all three siblings presented with CADASIL successively may appear disheartening, further studies are needed in order to control the clinical course of this devastating and unavoidable disorder.

The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study.

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene.