Alzheimer’s disease (AD) is rarely diagnosed before symptom onset, and accurate biomarkers of disease progression are limited, making clinical trial endpoints and success difficult to define. A new imaging method developed by a team of scientists at Yale University, New Haven, Connecticut, USA, allows synaptic loss to be examined, even before the onset of AD symptoms.
Visualisation of the loss of brain tissue or reduced brain metabolism in AD has been achievable by existing imaging technologies, but only in broad strokes. To clearly identify and examine changes in synaptic density in the early stages of AD, the researchers used PET imaging of a protein that is found in almost all brain synapses: SV2A.
In the study, [11C]UCB‐J PET was used to measure SV2A binding in 34 participants with early AD and 19 cognitively normal participants. Distribution volume ratio was calculated using a cerebellar reference region. When compared with cognitively normal participants, the researchers observed widespread reductions of SV2A binding in the medial temporal and neocortical regions of the brain in those with early AD. “These methods will allow us to examine synaptic loss at still earlier stages of disease – when people have evidence of Alzheimer’s pathogenesis but have not yet manifested symptoms,” said Prof Christopher van Dyck, Professor of Psychiatry, Neurology, and Neuroscience at Yale University and senior author of the study.
The distribution of synaptic damage, which is a more specific pathology present in the early stages of disease, could help monitor disease progression and the effect of potential therapeutic drugs. “This gives us confidence that we may use these results as a biomarker outcome for therapeutic trials, which could help speed development of new drugs to combat the disease,” said Dr Adam Mecca, assistant Professor of Psychiatry at Yale University and first author of the paper.