RT Journal Article
T1 Impaired Peripheral Lymphatic Function and Cerebrospinal Fluid Outflow in a Mouse Model of Alzheimer's Disease
A1 Kwon, Wu
A1 Moreno-Gonzalez, Ines
A1 Taylor-Presse, Kaithlyn
A1 Edwards, George
A1 Gamez, Nazaret
A1 Calderon, Olivia
A1 Zhu, Be
A1 Velasquez, Francisco C
A1 Soto, Claudio
A1 Sevick-Muraca, Eva Marie
A1 Taylor-Presse, 
K1 Alzheimer, Enfermedad de
AB Cerebrospinal fluid (CSF) outflow from the brain occurs through absorption into the arachnoid villi and, more predominantly, through meningeal and olfactory lymphatics that ultimately drain into the peripheral lymphatics. Impaired CSF outflow has been postulated as a contributing mechanism in Alzheimer's disease (AD). Herein we conducted nearinfrared fluorescence imaging of CSF outflow into the peripheral lymph nodes (LNs) and of peripheral lymphatic function in a transgenic mouse model of AD (5XFAD) and wild-type (WT) littermates. CSF outflow was assessed from change in fluorescence intensity in the submandibular LNs as a function of time following bolus, an intrathecal injection of indocyanine green (ICG). Peripheral lymphatic function was measured by assessing lymphangion contractile function in lymphatics draining into the popliteal LN following intradermal ICG injection in the dorsal aspect of the hind paw. The results show 1) significantly impaired CSF outflow into the submandibular LNs of 5XFAD mice and 2) reduced contractile frequency in the peripheral lymphatics as compared to WT mice. Impaired CSF clearance was also evidenced by reduction of fluorescence on ventral surfaces of extracted brains of 5XFAD mice at euthanasia. These results support the hypothesis that lymphatic congestion caused by reduced peripheral lymphatic function could limit CSF outflow and may contribute to the cause and/or progression of AD.
PB Sage Journals
YR 2019
FD 2019
LK https://hdl.handle.net/10630/37509
UL https://hdl.handle.net/10630/37509
LA eng
NO Kwon S, Moreno-Gonzalez I, Taylor-Presse K, et al. Impaired Peripheral Lymphatic Function and Cerebrospinal Fluid Outflow in a Mouse Model of Alzheimer’s Disease. Journal of Alzheimer’s Disease. 2019;69(2):585-593.
NO National Institute on Aging United States R56AG057581
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 26 ene 2026