Neuropathological characterization of two siblings carrying the MAPT S305S mutation demonstrates features resembling argyrophilic grain disease

Excerpt

Abnormal aggregation and accumulation of tau is a common feature of many neurodegenerative disorders, including Alzheimer disease (AD), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and argyrophilic grain disease (AGD). Tau protein is encoded by the MAPT gene and more than 40 pathogenic mutations in MAPT have been described in the AD & FTLD Mutation Database [1], including the MAPT p.S305S mutation (c.1920T>C), a silent mutation located in the last codon of exon 10 [2, 5, 6, 8]. The S305S mutation has been described in three affected siblings in a Scandinavian family with onset of symptoms in their early to mid-forties, and age at death between 52–59 years of age [5]. The clinical picture (early memory problems and behavioral changes including aggression as well as psychiatric and parkinsonian symptoms) has previously been reported [5], together with a neuropathological description of one S305S mutations carrier (Case II-2 in [5]) showing atrophy of the frontal and temporal lobes and tau pathology in neurons and glial cells [5]. In the present study, we performed a neuropathological analysis of an additional mutation carrier from the same family (Case II-4 in [5]), and compared the two siblings side-by-side by tau immunohistochemistry on formalin-fixed paraffin embedded sections using antibodies: AT8 (mouse monoclonal, 1:1000, Innogenetics), anti-tau pS422 (mouse monoclonal, 1:1,000, generated in-house at Roche), anti-3R tau (mouse monoclonal, RD3, 1:1,000, Upstate, Millipore) and anti-4R tau (mouse monoclonal, RD4, 1:1,000, Upstate, Millipore). …