The investigators used a linear mixed-effects model to estimate how astrocytosis, amyloid deposition, and glucose metabolism would change over time in the ADAD and sporadic Alzheimer’s disease groups. Comparing ADAD carriers to noncarriers, the model determined that amyloid began to aggregate in the putamen at about 17 years before symptom onset in carriers. Plaques subsequently spread outward, reaching the caudate nucleus and the anterior and posterior cingulate cortices by 15 years before symptom onset, and reaching the frontal cortex and other cortical regions at about 14 years before onset.
Conversely, the model found that DED binding in ADAD presymptomatic carriers steadily declined from its peak at about 20 years before expected symptom onset. By the time symptoms appeared, astrocyte activation was similar to that observed in noncarriers. Among patients with sporadic Alzheimer’s disease or MCI, the researchers found no significant temporal changes in DED binding.
Presymptomatic carriers also showed significant linear changes in glucose utilization. FDG uptake in the parietal and temporal regions began to decline at about seven years before symptom onset. Glucose metabolism was maintained in the caudate nucleus, thalamus, and hippocampus until it began to decline at about two years before symptom onset.
Patients with amyloid-positive MCI or sporadic Alzheimer’s disease showed significant temporal increases in amyloid deposition, and declines in glucose metabolism in the anterior cingulate cortex, but no significant changes in astrocyte activation.
“Possible explanations for this finding include the heterogeneity of disease stage in MCI patients, the shorter time span investigated in the sporadic patients compared to the ADAD participants, or a possibly different progression of astrocyte activation in the sporadic compared to the autosomal dominant forms,” said the authors.
—Michele G. Sullivan