Autosomal dominant early onset dementia and leukoencephalopathy in a japanese family : clinical, neuroimaging and genetic studies

Abstract We report here the results of clinical, neuroimaging and genetic studies of autosomal dominant dementia and leukoencephalopathy in a Japanese family. Twenty-two individuals in this family were examined clinically (17 living, 5 deceased), neuroradiologically and genetically (16 of 17 living members). Ten (5 deceased) of 22 individuals had early onset dementia (age of onset: 45.2 ± 12.1 years on average) and four of them had multiple white matter lesions and brain atrophy on brain MRI without history of brain ischemic attack. Another four individuals had abnormal white matter lesions on brain MRI without dementia. Linkage studies for chromosome 1q31–42, 14q24.3 and 21q21 responsible for Alzheimer's disease, chromosome 19p13.1–13.2 for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and chromosome 3 for familial non-specific dementia suggested no specific haplotypes cosegregated with the disease. Apo E genotypes were E2/2 and E2/3 in this family. Clinical, neuroimaging and genetic studies revealed that the disease in this family was distinguished from known familial dementia. This is the first report of a large Japanese family with autosomal dominant early onset dementia and leukoencephalopathy.