Elevated CSF soluble TIE-2 and reduced tissue TIE-2 expression are associated with tau pathology, blood-brain barrier leakiness, and cerebral hypoperfusion in Alzheimer's disease.
Observational
Yes
Elevated CSF and reduced tissue TIE-2 expression are associated with tau pathology, blood-brain barrier leakiness, and cerebral hypoperfusion in Alzheimer's disease.
Abstract Cerebral hypoperfusion and blood–brain barrier (BBB) leakiness are related to cognitive decline and the onset and spread of Aβ and tau pathology in Alzheimer's disease (AD). Disrupted angiopoietin/TIE (ANGPT/TIE) signalling causes neurovascular instability and BBB leakiness accelerating cognitive decline and disease pathology in mouse models of AD. To explore ANGPT/TIE signalling in human AD, we measured CSF TIE‐1 and TIE‐2 levels by ELISA in two independent clinical dementia cohorts, and serum and CSF Tie‐1/‐2 in paired CSF and serum samples from neurologically normal individuals. ANGPT1, ANGPT2, TIE‐1 and TIE‐2 levels were measured by ELISA in crude homogenate (CH) and microvessel‐enriched fractions (MVFs) of post‐mortem human parietal cortex in relation to biochemical markers of cerebral perfusion (MAG:PLP1) and BBB leakiness (parenchymal fibrinogen) in a control, AD, and vascular dementia (VaD) cohort. CSF soluble TIE‐2 was elevated in AD biomarker+ve individuals and correlated positively with CSF t‐tau and p‐tau, and markers of BBB leakiness, neuronal injury, and neuroinflammation. Tissue TIE‐2 levels were significantly reduced in Braak tangle stage (BS) III‐IV, that is, brains with early‐intermediate AD pathology, and were lower in MVFs in end‐stage AD pathology (BSV‐VI) than in controls or VaD. Lower levels of MVF TIE‐2 correlated with markers of cerebral hypoperfusion and BBB leakiness. Our study reveals a reciprocal relationship between elevated CSF and reduced tissue TIE‐2 expression that is related to markers of tau pathology, BBB leakiness, and cerebral hypoperfusion, providing novel insights into ANGPT/TIE signalling in AD.
Ince et al. (Sun,) conducted a observational in Alzheimer's disease. TIE-2 expression vs. Neurologically normal individuals / Controls was evaluated on CSF and tissue TIE-1 and TIE-2 levels. Elevated CSF soluble TIE-2 and reduced tissue TIE-2 expression are associated with tau pathology, blood-brain barrier leakiness, and cerebral hypoperfusion in Alzheimer's disease.