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. From there, plaques spread outward, reaching the caudate nucleus and the anterior and posterior cingulate cortices by 15 years before symptoms, and the frontal cortex and other cortical regions about 14 years before.
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 AD/MCI, there were 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 about 7 years before symptom onset. Glucose metabolism was maintained in the caudate nucleus, thalamus, and hippocampus until it began to decline about 2 years before symptom onset.
Patients with amyloid-positive MCI or sporadic Alzheimer’s 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,” the authors noted.
The research was supported by grants from Swedish government entities, various Swedish foundations, and GE Healthcare. The authors had no financial disclosures.