A young-onset dementia case associated with PDGFRβ mutation

Area of Science:

• Neurogenetics
• Vascular Biology
• Dementia Research

Background:

• Young-onset dementia (YOD) presents before age 65 and has diverse etiologies.
• Genetic factors are increasingly recognized in the pathogenesis of YOD.
• Platelet-derived growth factor receptor beta (PDGFRβ) plays roles in vascular development and homeostasis.

Observation:

• A 40-year-old male presented with progressive memory loss and disorientation, clinically resembling Alzheimer's disease.
• Brain imaging and cerebrospinal fluid analysis supported an Alzheimer's disease diagnosis.
• Whole-exome sequencing was performed to investigate potential genetic underpinnings.

Findings:

• A heterozygous missense variant, c.1316G>A (p.Arg439Gln), was identified in the PDGFRB gene.
• This PDGFRB variant is classified as likely pathogenic.
• The identified variant suggests a potential novel genetic link to vascular dysfunction contributing to cognitive decline.

Implications:

• This case suggests PDGFRB variants as a potential cause of YOD.
• Understanding the role of PDGFRβ in vascular health may reveal new therapeutic targets for dementia.
• Further research is warranted to explore the functional consequences of PDGFRB variants in cognitive aging.