Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy.

ABSTRACT: Alzheimer's disease (AD) is the most prevalent cause of dementia¹. Although there is no effective treatment for AD, passive immunotherapy with monoclonal antibodies against amyloid beta (Aβ) is a promising therapeutic strategy^2,3. Meningeal lymphatic drainage has an important role in the accumulation of Aβ in the brain⁴, but it is not known whether modulation of meningeal lymphatic function can influence the outcome of immunotherapy in AD. Here we show that ablation of meningeal lymphatic vessels in 5xFAD mice (a mouse model of amyloid deposition that expresses five mutations found in familial AD) worsened the outcome of mice treated with anti-Aβ passive immunotherapy by exacerbating the deposition of Aβ, microgliosis, neurovascular dysfunction, and behavio

SUBMITTER: Da Mesquita S 

PROVIDER: S-EPMC8817786 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature