Dapsone Combination Therapy Linked to Alzheimer Biomarker Changes in Single Lyme Disease Case Study

A newly published case report suggests that targeted antimicrobial therapy may influence Alzheimer disease–related biomarkers in a patient with chronic Lyme disease, although the findings remain preliminary and hypothesis-generating. Investigators reported that a short-course dapsone combination therapy (DCT) regimen was associated with reductions in phosphorylated tau (p-tau) and improvements in amyloid beta ratios, raising questions about the role of infection-driven neuroinflammation in select patients.¹

Published in the Journal of Alzheimer’s Disease Reports, the study represents a single-patient analysis and should be interpreted cautiously in the context of broader Alzheimer disease (AD) research, which continues to emphasize multifactorial pathophysiology including amyloid, tau, vascular, and inflammatory mechanisms.

Case Findings and Biomarker Changes

The report, led by Richard I Horowitz, MD, medical director of the Hudson Valley Healing Arts Center, described a 67-year-old woman with a 15-year history of chronic Lyme disease and multiple coinfections who underwent a 9-week oral DCT regimen. The protocol included dapsone, rifampin, azithromycin, tetracycline, and methylene blue, alongside supportive therapies.

Following treatment, investigators observed:

• A reduction in plasma p-tau217 from 0.33 pg/mL to 0.12 pg/mL (63% decrease; normalized range)
• Improvement in amyloid-ß 42/40 ratio from 0.185 to 0.216
• Reduction in rheumatoid factor from 20 IU/mL to within normal limits

These biomarker changes were accompanied by patient-reported improvements in cognition, including memory recall and concentration, as well as reduced joint symptoms.

Repeat laboratory testing conducted 2–3 months post-treatment confirmed normalization of inflammatory and neurodegenerative markers, including sustained reductions in p-tau217 and stable amyloid ratios.

Mechanistic Context and Hypothesis

The authors proposed that persistent infection with Borrelia burgdorferi may contribute to neuroinflammatory processes linked to AD pathology, citing prior work demonstrating co-localization of spirochetes with amyloid plaques and tau in postmortem tissue.

Within this framework, DCT is hypothesized to target biofilm and persister forms of the organism, potentially reducing inflammatory triggers associated with tau phosphorylation and amyloid dynamics. Additional proposed mechanisms include modulation of inflammasome signaling and downstream neuroimmune pathways.

In the study discussion, the authors noted that, “This is the first case study showing that a short-term biofilm/persister drug regimen can potentially improve pathological triggers of neuroinflammation, including p-tau and amyloid-related biomarkers.”

However, they also acknowledged that AD is widely understood as a multifactorial condition, with infection representing only one of many proposed contributors, alongside genetic, metabolic, vascular, and environmental factors.

Clinical Context and Limitations

Despite the biologic signal observed, the findings are limited by the inherent constraints of a single case study. The authors emphasized that results are not generalizable and require validation in controlled clinical trials.

Current clinical guidelines from organizations such as the Infectious Diseases Society of America and the American Academy of Neurology do not recommend routine Lyme disease testing in patients with dementia, reflecting a lack of definitive causal evidence linking infection to Alzheimer disease progression.²

Additionally, prior randomized trials evaluating antimicrobial therapy in post-treatment Lyme disease syndrome have produced mixed or negative results, underscoring the complexity of attributing neurologic outcomes to infectious etiologies alone.³

The study also did not include longitudinal cognitive testing or imaging correlates, leaving uncertainty regarding the durability and clinical significance of the observed biomarker changes.

Broader Implications

While exploratory, the report contributes to an evolving body of literature examining the role of neuroinflammation and systemic contributors in neurodegenerative disease. Blood-based biomarkers such as p-tau217 have emerged as increasingly sensitive indicators of Alzheimer pathology, with strong associations to amyloid burden and future cognitive decline.

The authors call for larger, placebo-controlled studies to evaluate whether antimicrobial or anti-inflammatory strategies could have a role in specific patient subgroups, particularly those with overlapping infectious or inflammatory conditions.

Until such data are available, the findings are best viewed as hypothesis-generating rather than practice-changing, highlighting the need for continued investigation into the complex and heterogeneous drivers of AD.

REFERENCES
1. Horowitz RI. Improving biomarkers of inflammation including phosphorylated tau in a patient with chronic Lyme disease/post-treatment Lyme disease syndrome using dapsone combination therapy: A case study and literature review. J Alzheimers Dis Rep. 2026. doi:10.1177/25424823261445434
2. Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice guidelines for the prevention, diagnosis, and treatment of Lyme disease. Arthritis Care Res (Hoboken). 2021;73(1):1-9. doi:10.1002/acr.24117
3. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003. doi:10.1212/01.wnl.0000284604.61160.2d