認知症

An Update on Hereditary Dementias

メンデル遺伝形式を呈する認知症は，病型に対応した原因遺伝子が同定されている。遺伝学的検査により原因遺伝子に病的バリアントが同定されれば，臨床診断が確定できることから，遺伝性認知症に対する遺伝学的検査は臨床的意義を有する。顕性遺伝性アルツハイマー病や遺伝性前頭側頭型認知症の脳内病理を反映するバイオマーカーが開発されたことを契機に，遺伝性認知症を対象とした分子標的薬を用いた臨床試験が行われている。

Abstract

Causative genes associated with Mendelian-inherited subtypes of hereditary dementia with Mendelian inheritance have been identified. However, the clinical diagnosis of hereditary dementia remains challenging due to the substantial overlap among subtypes and diverse clinical presentations. A definitive diagnosis can be established when genetic testing detects a pathogenic variant in the corresponding gene. Biomarker changes indicative of pathological brain alterations, even before symptom onset, have been identified in dominantly inherited Alzheimer's disease and hereditary frontotemporal dementia. Against this background, clinical trials have been conducted to evaluate disease-modifying drugs, including anti-amyloid-β and anti-tau antibodies, as well as gene therapy for hereditary dementias.