Dear Editor:
We are writing to share our recent progress in exploring the therapeutic potential of lymphatic
reconstruction for the treatment of Alzheimer's disease. Our team at Cleveland Clinic has made
significant strides in exploring the lymphatic system’s role in brain disorders and the possibility
of treating brain conditions previously considered untreatable.1
Our research on lymphedema reconstruction of the arms, legs, and trunk led us to observe the
catchment effect2 and systemic effect3. These effects demonstrate that the lymphatic system
responds to surgical treatment as a unified organ, which means that lymphatic surgery remains
effective whether it is done at the problem site or elsewhere. Combining these observations with
the discovery of glymphatic4 and meningeal lymphatic5 dysfunction in Alzheimer's disease and
other neurodegenerative proteinopathies, we hypothesized that extra-cranial supermicrosurgical
lymphatic reconstruction may ‘de-clog’ the brain to improve the above conditions.
We were pleased to find that we were not alone in our thinking. Dr. Qingping Xie has also
explored similar hypotheses and has successfully performed 50 cases of such reconstruction on
patients with Alzheimer’s disease, with a mean follow-up period of 9 months. He observed
remarkable improvements in behavior, cognitive function, and memory (Video 1), as
demonstrated by the Minimum Mental State Examination (MMSE) and Montreal Cognitive
Assessment (MoCA). Although impressive, we recognize the need for more objective,
quantitative evidence, including biomarker measurements, imaging studies, and
neuropsychological evaluations, to support the efficacy of this procedure.
Currently, we are conducting animal studies to assay Alzheimer's disease biomarkers before and
after extra-anatomic supermicrosurgical lymphatic reconstruction using an established murine
Alzheimer disease model. These studies will provide critical evidence on whether lymphatic
reconstruction can indeed treat Alzheimer's disease. In parallel, Dr. Xie will continue his IRB-approved study on human subjects, following a protocol developed jointly with our
multidisciplinary team, including lymphatic supermicrosurgeons, neuroscientists, neurologists,
neuro-radiologists and neurosurgeons. By combining data from basic science and animal, and
human studies, we hope to arrive at a more definitive conclusion in the near future.
Our findings have significant implications for both plastic surgeons and humanity. For plastic
surgeons, this means expanding our scope of practice to brain disorders, creating new
procedures, and establishing a new subspecialty - brain lymphatic reconstruction surgery. For
humanity, we will likely be able to treat conditions previously considered untreatable, providing
hope and help to a patient population with limited options.
We acknowledge that our findings are preliminary, and the study is still ongoing. However, we
remain committed to pursuing this research with rigor and diligence and are optimistic about the
promise of lymphatic reconstruction for brain disorders.
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