Anti-mGluR5 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 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 two years. She was diagnosed with rapidly progressive AD and treated with donepezil and memantine without improvement. Initial workup showed hippocampal neurodegeneration on MRI/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 two weeks. Conclusion: This case demonstrates that anti-mGluR5 autoimmune encephalitis (AE) can manifest with a biomarker profile highly suggestive of AD, leading to prolonged misdiagnosis. It underscores the importance of considering autoimmune encephalitis in treatment-refractory or atypical dementia, even in the presence of supportive AD biomarkers, and highlights the potential for significant recovery with timely immunotherapy.