Estimating the synaptic density deficit in Alzheimer's disease using multi-contrast CEST imaging.

Area of Science:

• Neuroscience
• Biochemistry
• Medical Imaging

Background:

• Alzheimer's disease (AD) pathology involves synaptic degradation and neuronal loss.
• Noninvasive in vivo imaging of neurometabolites is essential for understanding neurodegenerative diseases.
• Magnetic resonance (MR) techniques like CEST and MRS offer insights into neurometabolite changes related to AD.

Purpose of the Study:

• To evaluate the sensitivity of cerebral metabolites to beta-amyloid (Aβ) induced synaptic deficit in an AD mouse model.
• To assess the feasibility of CEST and MRS for identifying and tracking pathophysiological mechanisms in AD.
• To investigate neurometabolite alterations in the hippocampus of the ARTE10 AD mouse model.

Main Methods:

• Chemical Exchange Saturation Transfer (CEST) and short echo time single voxel Magnetic Resonance Spectroscopy (MRS) were performed on a 9.4 Tesla small animal MR system.
• CEST spectra were acquired with varying radiofrequency (RF) saturation amplitudes to generate creatine-weighted and glutamate-weighted apparent exchange-dependent relaxation (AREX) maps.
• MRS quantified neurometabolites in the hippocampus, and data were analyzed in ARTE10 AD mice and wild-type (WT) littermates.

Main Results:

• Significant reductions in glutamate-AREX (Glu-AREX) and creatine-AREX (Cr-AREX) were observed in ARTE10 mice compared to WT.
• MRS revealed decreased glutamate (Glu) and Glu/tCr ratio, alongside increased total creatine (tCr), phosphocreatine (PCr), and glutathione (GSH) in ARTE10 mice.
• Glu-AREX and Cr-AREX positively correlated with the Glu/tCr ratio, suggesting links to synaptic function and energy metabolism.

Conclusions:

• CEST and MRS can detect Aβ-mediated synaptic degradation and alterations in neurotransmitter and energy metabolism in the hippocampus.
• These MR techniques are feasible for identifying and monitoring complex compensatory and pathological mechanisms in Alzheimer's disease in vivo.
• The findings support the role of neurometabolite changes in the pathophysiology of Alzheimer's disease.