MIND MAPS: Molecular imaging of the mitochondrial‐endoplasmic reticulum‐synaptic axis in patients with Alzheimer's spectrum disorders

Abstract

AbstractBackgroundNeurodegeneration is a pathognomonic feature of a variety of CNS disorders, including ALzhemimer's diosease. A dysfucntion of the mitochondrial‐endoplasmic reticulum‐synaptic axis is found in a variety of neurodegenerative disorders and has been linked to other pathological features such as misfolded protein accumulation, neuroinflammation, dysfunction of neurotransmitter release and neuronal loss.MethodWe examined a 12 patients with Alzheimer's spectrum disorder (ASD, MMSE range 16‐29) at baseline and 12‐18 months later with three PET radioligands; [18f]BCPP‐EF, [11C]SA4503 and [11C]UCB‐J, highly specific molecular markers of the mitochondrial complex 1 (MC1), the sigma 1 receptor (s1R) and the synaptic vesicular glycoprotein 2A (SV2A). The baseline data from the patient group was compared to a group of 16 age matched healthy volunteers.ResultWe found significant differences between the patient group and healthy volunteers for all three molecular markers in multiple brain regions. In addition, changes in mitochondrial markers were seen in the cortical areas of patients over the period of 12‐18 month.ConclusionMarkers of disruption of the mitochondrial‐endoplasmic reticulum‐synaptic axis can be detected in ASD patients in vivo, and can be demonstrated to change over a period of 12 ‐18 months. The imaging of multiple molecular markers enhances the evaluation of neurodegeneration pathology. Ashwin V. Venkataraman, Gaia Rizzo, and the MIND MAPS Consortium