Details

Autor(en) / Beteiligte

• Spillantini, Maria Grazia
• Murrell, Jill R.
• Goedert, Michel
• Farlow, Martin R.
• Klug, Aaron
• Ghetti, Bernardino

Titel

Mutation in the Tau Gene in Familial Multiple System Tauopathy with Presenile Dementia

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1998-06, Vol.95 (13), p.7737-7741

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Familial multiple system tauopathy with presenile dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose genetic basis is unknown. We now report a G to A transition in the intron following exon 10 of the gene for microtubule-associated protein tau in familial MSTD. The mutation is located at the 3′neighboring nucleotide of the GT splice-donor site and disrupts a predicted stem-loop structure. We also report an abnormal preponderance of soluble tau protein isoforms with four microtubule-binding repeats over isoforms with three repeats in familial MSTD. This most likely accounts for our previous finding that sarkosyl-insoluble tau protein extracted from the filamentous deposits in familial MSTD consists only of tau isoforms with four repeats. These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments. The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer's disease and other tauopathies.