Anti-Metabotropic Glutamate Receptor 5 Autoimmune Encephalitis with a Typical Alzheimer's Disease Biomarker Profile: A Case of Rapidly Progressive Dementia Unresponsive to Cholinesterase Inhibitors.

INTRODUCTION

The distinction between neurodegenerative and autoimmune causes of rapidly progressive dementia can be challenging, particularly when atypical Alzheimer's disease (AD) biomarkers are present. We present a case of anti-metabotropic glutamate receptor 5 (mGluR5) autoimmune encephalitis (AE) initially misdiagnosed as AD due to concordant clinical, imaging, and biomarker findings.

CASE PRESENTATION: A 51-year-old woman developed progressive memory decline, apathy, and stereotyped paper-folding behavior over 2 years. She was diagnosed with rapidly progressive AD and treated with donepezil and memantine without improvement. Initial workup showed hippocampal neurodegeneration on magnetic resonance imaging/MRS and elevated plasma phosphorylated tau181, tau217, and GFAP - consistent with an AD biomarker profile. Neurological examination later revealed bilateral pyramidal signs. Re-evaluation identified serum anti-mGluR5 antibodies. Treatment with intravenous methylprednisolone and immunoglobulin led to marked improvement in cognition and behavior within 2 weeks.

CONCLUSION

This case demonstrates that anti-mGluR5 AE can manifest with a biomarker profile highly suggestive of AD, leading to prolonged misdiagnosis. It underscores the importance of considering AE in treatment-refractory or atypical dementia, even in the presence of supportive AD biomarkers, and highlights the potential for significant recovery with timely immunotherapy.