2 research outputs found
Angiopep-2, an MRI Biomarker, Dynamically Monitors Amyloid Deposition in Early Alzheimer’s Disease
The reliable and dynamic detection of amyloid β-protein
(Aβ)
deposition using imaging technology is necessary for preclinical Alzheimer’s
disease (AD), which may significantly improve prognosis. The present
study aimed to evaluate the feasibility of applying angiopep-2 (ANG),
a chemical exchange saturation transfer-magnetic resonance imaging
(CEST-MRI) biomarker, for monitoring Aβ deposition in vivo.
ANG exerted a good chemical exchange saturation transfer (CEST) effect
and displayed a moderate binding affinity to Aβ1–42 in
vitro. Six-month-old mice with AD injected with ANG exhibited a significantly
enhanced CEST effect than controls in vivo; this effect gradually
became more apparent at 8, 10, and 12 months. Spatial learning impairment
caused by abundant Aβ deposition (representing mild cognitive
impairment in AD patients) develops at 12 months in APPswe/PSEN1dE9
(line 85) AD mice. To conclude, the CEST of ANG could display very
earlier age-related Aβ pathological progress in mice with AD,
consistent with immunohistochemistry. ANG has extraordinary potential
for clinical transformation as an imaging biomarker to diagnose early
AD and track its progress dynamically and nonradiationally
Amide Proton Transfer-Weighted Imaging Detects Hippocampal Proteostasis Disturbance Induced by Sleep Deprivation at 7.0 T MRI
Sleep deprivation leads to hippocampal injury. Proteostasis
disturbance
is an important mechanism linking sleep deprivation and hippocampal
injury. However, identifying noninvasive imaging biomarkers for hippocampal
proteostasis disturbance remains challenging. Amide proton transfer-weighted
(APTw) imaging is a chemical exchange saturation transfer technique
based on the amide protons in proteins and peptides. We aimed to explore
the ability of APTw imaging in detecting sleep deprivation-induced
hippocampal proteostasis disturbance and its biological significance,
as well as its biological basis. In vitro, the feasibility of APTw
imaging in detecting changes of the protein state was evaluated, demonstrating
that APTw imaging can detect alterations in the protein concentration,
conformation, and aggregation state. In vivo, the hippocampal APTw
signal declined with increased sleep deprivation time and was significantly
lower in sleep-deprived rats than that in normal rats. This signal
was positively correlated with the number of surviving neurons counted
in Nissl staining and negatively correlated with the expression of
glucose-regulated protein 78 evaluated in immunohistochemistry. Differentially
expressed proteins in proteostasis network pathways were identified
in the hippocampi of normal rats and sleep-deprived rats via mass
spectrometry proteomics analysis, providing the biological basis for
the change of the hippocampal APTw signal in sleep-deprived rats.
These findings demonstrate that APTw imaging can detect hippocampal
proteostasis disturbance induced by sleep deprivation and reflect
the extent of neuronal injury and endoplasmic reticulum stress