Patients with mild Alzheimer’s disease dementia or amnestic mild cognitive impairment due to Alzheimer’s showed 41% less binding of an investigational PET imaging marker of synaptic density when compared with cognitively normal control patients.
“Synaptic loss in the association cortex and the limbic system is a robust and consistent pathology in AD [Alzheimer’s disease] and is closely correlated with cognitive impairment,” wrote Dr. Chen of Yale University, New Haven, Conn., and his associates. “However, until now, the assessment of synaptic density and the quantification of pre-synaptic proteins in AD could only be performed in postmortem brain tissues. The present study demonstrated, for the first time, that noninvasive PET imaging with 11C-UCB-J is capable of measuring reductions in synaptic density in vivo in the hippocampus of individuals with amnestic MCI [mild cognitive impairment] and AD dementia.”
The marker could potentially be used to identify early synaptic loss and track disease progression and therapeutic response, the authors suggested.
The team that created 11C-UCB-J, also known as ((R)-1-((3-(11C-methyl-11C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one), conducted this study. The agent binds to synaptic vesicle glycoprotein 2A (SV2A), which is the only one of three isoforms that is expressed only in brain synapses. The team’s earliershowed that SV2A is a marker of synaptic density and that 11C-UCB-J can effectively track changes in the glycoprotein’s presence.
The study comprised 5 patients with amnestic MCI due to AD, 5 with mild AD dementia, and 11 cognitively normal matched controls; they were a mean of 72 years old. All underwent amyloid PET scanning to confirm Alzheimer’s pathology, and then additional PET imaging with 11C-UCB-J.
In a model that corrected for age and brain atrophy, AD patients showed a 41% decrease in hippocampal binding with the agent. The decrease correlated positively with a composite score of episodic memory, the investigators noted.
Dr. Chen disclosed research support from Eli Lilly and Merck; two of his coauthors have a patent pending for a version of the agent.
SOURCE: Chen M-K et al. JAMA Neurol. 2018 July 16.