# Blood-brain barrier integrity and prevalence of intrathecal T helper 17.1 cells in Huntington´s disease

## TL;DR

This study explores the integrity of the blood-brain barrier in Huntington's disease and finds no significant evidence of leakage or pericyte involvement.

## Contribution

The study provides new insights into the absence of overt blood-brain barrier disruption in Huntington's disease gene-expansion carriers.

## Key findings

- No significant difference in Q-Alb was found between HDGECs and controls.
- Q-Alb increased in HDGECs over five years, but not significantly compared to controls.
- No association was found between Q-Alb and Th17.1 cells or PDGFR-β in HDGECs.

## Abstract

Blood-brain barrier (BBB) involvement in the pathogenesis of Huntington´s disease (HD) is not well understood. We previously demonstrated increased prevalence of T Helper 17.1 (Th17.1) cells in the cerebrospinal fluid (CSF) of HD gene-expansion carriers (HDGECs), which might indicate a dysfunction in the BBB or the blood-CSF barrier (BCB) in HD.

The aim of this exploratory study is to investigate whether the CSF/plasma albumin quotient (Q-Alb) and CSF platelet-derived growth factor-β (PDGFR-β) can be used as biomarkers for BBB/BCB integrity in HD and if there is an association between Q-Alb and the prevalence of intrathecal Th17.1 cells in HDGECs.

A total of 145 HDGECs and controls were included in the Q-Alb analysis. Forty-four of these individuals underwent a second lumbar puncture after five years and were included in the analysis of changes in Q-Alb over time. CSF from 33 HDGECs and controls was analysed for Th17.1 cells and CSF from 100 HDGECs and controls was analysed for PDGFR-β.

No significant difference for Q-Alb was found between the pre-motor manifest HDGECs, motor manifest HDGECs, and controls (p = 0.49). We found a significant increase in Q-Alb in HDGECs over the 5-year period (p = 0.014), but when compared with controls, no significant difference was found (p = 0.32). No significant association was found between Q-Alb and the prevalence of Th17.1 cells (p = 0.97) nor Q-Alb and PDGFR-β (p = 0.89) in HDGECs.

We found no evidence of increased BBB/BCB leakage of albumin in HDGECs compared to controls. Neither did we find signs of pericyte involvement as measured by PDGFR-β in HDGECs. These results suggest that overt BBB/BCB disruption may be limited in HDGECs. Future longitudinal studies should employ more sensitive methods like dynamic contrast-enhanced magnetic resonance imaging to evaluate region specific microleaks.