Homeostatic capabilities of the choroid plexus epithelium in Alzheimer's disease

Abstract

As the secretory source of vitamins, peptides and hormones for neurons, the choroid plexus (CP) epithelium critically provides substances for brain homeostasis. This distributive process of cerebrospinal fluid (CSF) volume transmission reaches many cellular targets in the CNS. In ageing and ageing-related dementias, the CP-CSF system is less able to regulate brain interstitial fluid. CP primarily generates CSF bulk flow, and so its malfunctioning exacerbates Alzheimers disease (AD). Considerable attention has been devoted to the blood-brain barrier in AD, but more insight is needed on regulatory systems at the human blood-CSF barrier in order to improve epithelial function in severe disease. Using autopsied CP specimens from AD patients, we immunocytochemically examined expression of heat shock proteins (HSP90 and GRP94), fibroblast growth factor receptors (FGFr) and a fluid-regulatory protein (NaK2Cl cotransporter isoform 1 or NKCC1). CP upregulated HSP90, FGFr and NKCC1, even in end-stage AD. These CP adjustments involve growth factors and neuropeptides that help to buffer perturbations in CNS water balance and metabolism. They shed light on CP-CSF system responses to ventriculomegaly and the altered intracranial pressure that occurs in AD and normal pressure hydrocephalus. The ability of injured CP to express key regulatory proteins even at Braak stage V/VI, points to plasticity and function that may be boosted by drug treatment to expedite CSF dynamics. The enhanced expression of human CP 'homeostatic proteins' in AD dementia is discussed in relation to brain deficits and pharmacology.

Nationwide hospital‐based survey of idiopathic normal pressure hydrocephalus in Japan: Epidemiological and clinical characteristics

“…The primary pathologic change in iNPH is disturbed CSF circulation (Johanson et al., 2004), for which CSF shunt operations are primarily performed (Kazui, Miyajima, Mori, & Ishikawa, 2015). While a study demonstrated the effectiveness of LP shunting in 2015 (Kazui et al., 2015), the selection is presently made according to the patient's condition and surgeon's experience (Anderson, Grant, de la Paz, Frucht, & Goodman, 2002; Klinge, 2012; Klinge, Hellstrom, Tans, & Wikkelso, 2012; Klinge, Marmarou, Bergsneider, Relkin, & Black, 2005).…”

Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of Multiple Sclerosis and Alzheimer’s Disease?

“…The choroid plexus is a highly vascularized tissue that is present in all brain ventricles, and whose primary function is the production and renewal of the main constituents of the CSF (Johanson et al, 2004; Liddelow et al, 2012). The inner stroma of the choroid plexus is richly irrigated by fenestrated capillaries (Wolburg and Paulus, 2010), allowing the free passage of circulating molecules and immune cells, into this compartment.…”

“…Under healthy conditions, however, the blood-CSF barrier (BCSFB) formed by the choroid plexus epithelial cells restricts immune-cell entry into the CSF and the brain parenchyma (Baruch and Schwartz, 2013; Engelhardt et al, 2001; Hasegawa-Ishii et al, 2013). AD patients exhibit major alterations in choroid plexus structure and morphology, as well as in epithelial cell function, attributable mainly to the increase in toxic Aβ peptides (Brkic et al, 2015; Johanson et al, 2004; Vargas et al, 2010). In addition, the ability of epithelial cells to express the transporters that participate in Aβ efflux, as well as to secrete Aβ-scavenging proteins into the CSF and their corresponding receptors, decreases with age and is compromised in different in-vitro and in-vivo models of AD (Antequera et al, 2009; Crossgrove et al, 2005; Zlokovic et al, 1996).…”

18F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus Signal

“…CP consists of a dense collection of capillaries in an ependymal stroma surrounded by a layer of epithelium [12]. The CP of the lateral ventricles contain several materials that could possibly bind to FTP, including melanin [13], calcification/mineralization [14], Biondi rings [15, 16], and iron deposits [17]. Monoamine oxidase A has also been cited as a source of off-target binding [10, 18].…”