Familial Behavioral Variant Frontotemporal Dementia Associated With Astrocyte-Predominant Tauopathy

摘要: A familial behavioral variant frontotemporal dementia associated with astrocyte-predominant tauopathy is described in 2 sisters born from consanguineous parents. The neuropathologic examination revealed massive accumulation of abnormally hyperphosphorylated, conformational, truncated tau at aspartic acid 421, ubiquitinated and nitrated Tyr29 cortical astrocyte (including their perivascular foot processes), Bergmann glia. Smaller amounts abnormal were observed neurons rarely oligodendrocytes. There was decreased expression glial glutamate transporter the majority tau-positive astrocytes. Gel electrophoresis sarkosyl-insoluble fractions showed bands 64 60 kDa a doublet 67 to 70 (which are different those seen Alzheimer disease typical 4R 3R tauopathies) together several lower molecular weight indicative tau. Analysis MAPT isoforms further altered splicing representation involving exons 2, 3, 10. Genetic testing no known mutations PSEN1, PSEN2, APP, MAPT, GRN, FUS, TARDBP pathologic expansion C9ORF72. However, novel rare heterozygous sequence variant(p.Q140H) uncertain significance identified FUS both siblings.