Choroid Plexus in Alzheimer's Disease-The Current State of Knowledge

Abstract

The choroid plexus (CP), located in each of the four ventricles of the brain, is formed by a monolayer of epithelial cells that surrounds a highly vascularized connective tissue with permeable capillaries. These cells are joined by tight junctions forming the blood-cerebrospinal fluid barrier (BCSFB), which strictly regulates the exchange of substances between the blood and cerebrospinal fluid (CSF). The primary purpose of the CP is to secrete CSF, but it also plays a role in the immune surveillance of the central nervous system (CNS) and in the removal of neurotoxic compounds from the CSF. According to recent findings, the CP is also involved in the modulation of the circadian cycle and neurogenesis. In diseases such as Alzheimer's disease (AD), the function of the CP is impaired, resulting in an altered secretory, barrier, transport, and immune function. This review describes the current state of knowledge concerning the roles of the CP and BCSFB in the pathophysiology of AD and summarizes recently proposed therapies that aim to restore CP and BCSFB functions.

Keywords: Alzheimer’s disease; barrier disruption; blood–cerebrospinal fluid barrier; choroid plexus; neurodegenerative disorder; novel therapies.

Figure 1

Schematic representation of the blood–brain barrier (BBB) and blood–cerebrospinal fluid barrier (BCSFB), depicting the cellular constituents of each barrier.

Figure 2

The choroid plexus (CP) and the blood–cerebrospinal barrier (BCSFB). The zoom highlights the alterations occurring in AD: (1) cell morphology—CP epithelial cell (CPEC) flattening and increased thickness and irregularity of the basement membrane; (2) immune system—impairment of leukocyte trafficking and decreased IFN-γ signaling; (3) transporters and integrity—tight junction disruption and deregulation of transporters of amyloid-β peptide (Aβ); (4) CSF secretion—diminished AQP1 expression, decreased secretion of CSF proteins, and increased production of Aβ in the CP; (5) metabolism—mitochondrial dysfunction and increased nitric oxide (NO) and reactive oxygen species (ROS) levels, and caspase-3 and -9 expression; (6) deposits—deposits of Aβ, lipofuscin granules, and Biondi ring tangles accumulate in CPECs.