ABSTRACT
The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity of the brain's resident immune cells, microglia. Here we used [11C]DPA-713 and positron emission tomography to quantify the 18 kDa translocator protein, a marker of activated microglia or reactive astrocytes, in the brains of patients with post-treatment Lyme disease symptoms of any duration compared to healthy controls. Genotyping for the TSPO rs6971 polymorphism was completed, and individuals with the rare, low affinity binding genotype were excluded. Data from eight brain regions demonstrated higher [11C]DPA-713 binding in 12 patients relative to 19 controls. [11C]DPA-713 PET is a promising tool to study cerebral glial activation in PTLDS and its link to cognitive symptoms.
Subject(s)
Acetamides/pharmacokinetics , Brain/diagnostic imaging , Lyme Neuroborreliosis/diagnostic imaging , Positron-Emission Tomography , Pyrazoles/pharmacokinetics , Pyrimidines/pharmacokinetics , Adolescent , Adult , Aged , Apoptosis Regulatory Proteins/genetics , Brain/drug effects , Carbon Radioisotopes/pharmacokinetics , Cognition Disorders/diagnostic imaging , Cognition Disorders/etiology , Female , Humans , Image Processing, Computer-Assisted , Lyme Neuroborreliosis/genetics , Magnetic Resonance Imaging , Male , Membrane Proteins/genetics , Middle Aged , Neuropsychological Tests , Pilot Projects , Polymorphism, Genetic/genetics , Severity of Illness Index , Young AdultABSTRACT
Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.