Work

Elucidating cortical neurovascular involvement in Huntington's disease using human brain tissue microarrays

Year: 2025

Type: article

Abstract: Although the genetic basis of Huntington's disease (HD) has been determined, the underlying pathophysiological mechanisms contributing to neurodegeneration remain largely unknown. In recent years, increasing evidence has posited vascular dysfunction as a significant early event in disease pathogenesis; however, these processes remain to be fully elucidated. High-content immunohistochemical screening studies were conducted on HD middle temporal gyrus (MTG) human brain tissue microarrays (TMAs) to investigate various components of the vascular system, including endothelial cells (UEA-1), pericytes (PDGFRβ), vascular smooth muscle cells (αSMA), extracellular matrix components (ECM; collagen IV and fibronectin), and leakage markers (haemoglobin and fibrinogen). Analyses of vascular markers revealed an increase in the number of vessels in the HD TMA cohort which was associated with advancing striatal pathology and earlier symptom onset. Furthermore, our findings highlight the preservation of pericytes, vascular smooth muscle cells, ECM components, and blood-brain barrier integrity in the HD MTG. Collectively, the TMA findings allude to mild vascular remodelling in the temporal cortex which is known to present with a lesser degree of neuronal degeneration in HD. • Vascular remodelling in the HD temporal cortex is widely influenced by endothelial cells. • Altered HD vasculature may not stem from overt perivascular cell loss. • PDGFRβ internalisation is unaffected in HD pericytes. • Extracellular matrix and BBB integrity remain intact in the HD cerebral cortex.

Source: Neurobiology of Disease

DOI: 10.1016/j.nbd.2025.106829