Details

Autor(en) / Beteiligte

• Hamasaki, Hideomi
• Maeda, Norihisa
• Sasagasako, Naokazu
• Honda, Hiroyuki
• Shijo, Masahiro
• Mori, Shin-Ichiro
• Yagita, Kaoru
• Arahata, Hajime
• Iwaki, Toru

Titel

Neuropathology of classic myotonic dystrophy type 1 is characterized by both early initiation of primary age-related tauopathy of the hippocampus and unique 3-repeat tauopathy of the brainstem

Ist Teil von

• Journal of neuropathology and experimental neurology, 2023-01, Vol.82 (1), p.29-37

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Myotonic dystrophy type 1 (DM1) is an inherited autosomal-dominant condition that induces altered splicing of transcripts, including MAPT, leading to a distinctive abnormal deposition of tau protein in the CNS. We characterized the tau isoforms of abnormal depositions in the brains of 4 patients with classic DM1 by immunohistochemistry using isoform-specific antibodies. All patients, including those of presenile age, showed numerous neurofibrillary tangles (NFTs) of both 3-repeat and 4-repeat tau in the limbic area and mild involvement in the cerebral cortex. Amyloid-β deposition was only seen in 1 senile case while cortical tauopathy in all other cases was consistent with primary age-related tauopathy (PART). In the putamen and globus pallidus, only a few tau deposits were observed. Tau deposits in the brainstem frequently showed a DM1-specific pattern with 3-repeat tau dominant NFTs. Additionally, tau-positive astrocytes morphologically similar to tufted astrocytes and astrocytic plaques were occasionally observed in the brainstem; however, they were predominantly composed of 3-repeat tau. Thus, the classic DM1 showed both early onset of PART-like pathology in the limbic areas as a progeroid syndrome of DM1 and an abnormal splicing event in the brainstem leading to 3-repeat tau dominant accumulation with both neuronal and astrocytic involvement.