Affiliations: [a] Banco de Tejidos, Fundación CIEN (FCIEN-ISCIII), Madrid, Spain | [b] Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain | [c] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), Spain | [d] Unidad de Encefalopatías Espongiformes, Unidad Funcional de Investigación en Enfermedades Crónicas, (UFIEC-ISCIII), Madrid, Spain
Correspondence:
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Correspondence to: Alberto Rábano, Departamento de Neuropatología y Banco de Tejidos, Fundación CIEN, c/ Valderrebollo, 5, 28031 Madrid, Spain. Tel.: +34 91 385 22 00; Fax: +34 91 385 21 18; E-mail: [email protected].
Abstract: Argyrophilic grain disease (AGD) is a sporadic 4 R tauopathy that usually presents in combination with other sporadic tauopathies or with Alzheimer's disease (AD) pathology, and may contribute to dementia in older age patients. In previous studies, a detailed analysis of AGD pathology in the medial temporal lobe has been hampered by the common presence of concurrent AD changes. With the objective to assess the potentiality of AGD in research on tau propagation, here we present a study of a series of AGD postmortem cases (n = 53). The total series was divided in a subgroup of cases with Braak-stage ≤ II (n = 23) and a subgroup with Braak-stage>II or indeterminate (n = 30) in order to minimize interference with AD pathology. A detailed neuropathological evaluation of the medial temporal lobe was performed at three coronal levels with Gallyas stain, and immunostains with p62, AT8, and AT100 antibodies. Western blot analysis of the entorhinal and hippocampal cortex was performed in 8 cases with a panel of anti-tau antibodies. Cases were genotyped for APOE polymorphism and for H1/H2 alleles of the MAPT gene. All cases, and particularly lower Braak-stage cases, displayed a highly homogeneous pattern of involvement by argyrophilic grains and pretangles between connected regions (primarily basolateral nuclei of the amygdala, entorhinal/transentorhinal cortex, and hippocampal cortex). Staging of cases reveals progression of pathology along well-established neuroanatomical pathways. Western blot studies yielded a specific pattern of isoforms with a characteristic predominant band at 64 kDa. Genetic analysis showed a strong association with the H1 allele of the MAPT gene. AGD may thus be an optimal natural disease model for testing hypotheses related to tau propagation in human tissue.
