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. Issue 1 (4th November 2022)

• Record Type: Journal Article
• Authors: Hamasaki, Hideomi; Maeda, Norihisa; Sasagasako, Naokazu; Honda, Hiroyuki; Shijo, Masahiro; Mori, Shin-Ichiro; Yagita, Kaoru; Arahata, Hajime; Iwaki, Toru
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 82:Issue 1(2023)
• Page Start: 29
• Page End: 37
• Publication Date: 2022-11-04
• Subjects: Astrocyte -- Myotonic dystrophy -- Progeria -- RNA splicing -- Tau protein -- Tauopathy; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlac097
• Languages: English
• ISSNs: 0022-3069

Abstract

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.