A Proposed Role for Lymphatic Supermicrosurgery in the Management of Alzheimer's Disease: A Primer for Reconstructive Microsurgeons

Abstract

The relatively recent discovery of a novel lymphatic system within the brain meninges has spurred interest in how waste products generated by neurons and glial cells-including proteins associated with Alzheimer's disease (AD) pathology such as amyloid beta (Aβ) and tau-are disposed of. Evidence is building that suggests disease progression in AD and other cognitive impairments could be explained by dysfunction in the brain's lymphatic system or obstruction of drainage. An interesting implication of this hypothesis is that, by relieving the obstruction of flow, lymphatic reconstruction along the drainage pathway could serve as a potential novel treatment. Should this concept prove true, it could represent a surgical solution to a problem for which only medical solutions have thus far been considered. This study is meant to serve as a primer for reconstructive microsurgeons, introducing the topic and current hypotheses about the potential role of lymphatic drainage in AD. A preview of current research evaluating the feasibility of lymphatic reconstruction as a surgical approach to improving Aβ clearance is provided, with the aim of inspiring others to design robust preclinical and clinical investigations into this intriguing hypothesis.

Keywords: Alzheimer's disease; glymphatic system; intramural periarterial drainage; lymphatic reconstruction; lymphovenous anastomosis; meningeal lymphatic system; supermicrosurgery.

Fig. 1

A simplified schematic of the waste clearance and drainage pathway. Waste products such as metabolic products, cellular debris, and degraded or misfolded proteins are collected in the interstitial fluid (ISF) within the brain parenchyma. Through an as-yet debated pathway, the waste is exchanged between the ISF and cerebrospinal fluid (CSF) in the subarachnoid space. The CSF and waste then travel into the meningeal lymphatics, which drain to the deep cervical lymph nodes and then out to the peripheral circulation. (The images of the skull and brain were designed by Freepik and are available for free.)