INVESTIGATING THE BLOOD-CSF BARRIER IN ALZHEIMER’S DISEASE: AΒ TRANSPORT AND BARRIER INTEGRITY IN A TRIPLE TRANSGENIC MURINE MODEL

According to the World Health Organization, 57 million people worldwide are affected by dementia, and Alzheimer’s disease (AD) accounts for 60–70% of these cases, rendering it a major public health concern. Even though the neurobiological mechanisms are not yet completely understood, AD is characterized by the extracellular accumulation of amyloid-β (Aβ) peptide in the form of plaques and by the intracellular formation of neurofibrillary tangles containing hyperphosphorylated Tau protein (pTau). Moreover, AD pathophysiology involves alterations of the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). The mechanisms governing Aβ exchange between the blood and the brain are multiple and bidirectional, and its pathological accumulation notably results from impaired cerebral clearance. Clinically, Aβ and pTau proteins are detectable in the cerebrospinal fluid, highlighting the involvement of the BCSFB in the elimination of these neurotoxic compounds. We here investigate the functional integrity of the BCSFB using a triple transgenic murine model (3xTgAD) of AD and post mortem approaches such as tissue clearing, laser microdissection and droplet digital PCR (ddPCR). Our preliminary results from the analysis of anatomo-functional components of the BCSFB suggest significant alterations in the expression of several structural and functional components at the level of the choroid plexuses, the main anatomical site of the BCSFB. These findings open promising perspectives for a better understanding of the involvement of the BCSFB in the pathophysiology of AD.