A novel PSEN1 (p.Gln223Leu) variant associated with spastic paraparesis and early-onset Alzheimer's disease

Journal of Alzheimer s Disease Reports 2026 Open access

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Authors: Hyuk-je Lee, Hansol Im, Bora Yoon, YongSoo Shim, Dongju Won, Jung Hwan Lee
DOI: 10.1177/25424823261419068
Cited by: 0
References: 32

Abstract

We report a novel PSEN1 likely pathogenic variant associated with spastic paraparesis (SP) preceding cognitive decline. A 41-year-old man with a two-year history of SP followed by cognitive impairment one year later, was found to carry a heterozygous PSEN1 c.668A > T (p.Gln223Leu) variant. Alzheimer's disease (AD) was confirmed with a combination of low CSF Aβ 42 levels and amyloid positivity on [ 18 F]Florbetaben PET. This case represents the third reported association between substitutions at PSEN1 codon 223 and AD with SP, emphasizing the need to consider PSEN1 mutations in cases of SP preceding cognitive decline.

Fields of Study & Subjects

Alzheimer's disease research and treatments Dementia and Cognitive Impairment Research Hereditary Neurological Disorders

Publication details

Journal / source
Journal of Alzheimer s Disease Reports
Volume
10
Pages
25424823261419068–25424823261419068
Publication date
1 January 2026
Language
EN