Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion

Yoshiki Hase, Dan Jobson, Jeremy Cheong, Kelvin Gotama, Luciana Maffei, Mai Hase, Alhafidz Hamdan, Ren Ding, Tuomo Polvikoski, Karen Horsburgh, Raj N Kalaria

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Neurovascular unit mural cells called ‘pericytes’ maintain the blood-brain barrier and local cerebral blood flow.Pathological changes in the hippocampus predispose to cognitive impairment and dementia. The role of hippocampal pericytes in dementia is largely unknown. We investigated hippocampal pericytes in 90 postmortem brains from post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), and AD-VaD (Mixed) subjects, and post-stroke non-demented survivors as well as similar age controls. We used collagen IV immunohistochemistry to determine pericyte densities and a mouse model of VaD to validate the effects of chronic cerebral hypoperfusion. Despite increased trends in hippocampal microvascular densities across all dementias, mean pericyte densities were reduced by ~25–40% in PSD, VaD and AD subjects compared to those in controls, which calculated to 14.1 ± 0.7 per mm capillary length, specifically in the cornu ammonis (CA) 1 region (P = 0.01). In mice with chronic bilateral carotid artery occlusion, hippocampal pericyte loss was ~60% relative to controls (P < 0.001). Pericyte densities were correlated with CA1 volumes (r = 0.54, P = 0.006) but not in any other sub-region. However, mice subjected to the full-time environmental enrichment (EE) paradigm showed remarkable attenuation of hippocampal CA1 pericyte loss in tandem with CA1 atrophy. Our results suggest loss of hippocampal microvascular pericytes across common dementias is explained by a vascular aetiology, whilst the EE paradigm offers significant protection.
Original languageEnglish
Article number29
Pages (from-to)1-14
JournalActa Neuropathologica Communications
Volume12
DOIs
Publication statusPublished - 15 Feb 2024

Keywords / Materials (for Non-textual outputs)

  • Alzheimer’s disease
  • Brain capillary
  • Collagen IV or COL4
  • Dementia
  • Hippocampus
  • Pericyte
  • Vascular dementia

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