Leo & Llibre-Guerra's comparison of sporadic vs genetic AD is out!

Leonardo Iaccarino and Jorge J. Llibre-Guerra led a manuscript comparing amyloid (PiB) and glucose (FDG) PET uptake in sporadic Early-Onset Alzheimer's Disease (sEOAD) against Dominantly Inherited Alzheimer's Disease (DIAD).

The study included 134 sEOAD (mean age 60yo), 89 DIAD (46yo) and 102 controls (45yo). All participants underwent cognitive screening, FDG, PiB, and MRI scans. Both sEOAD and DIAD participants were symptomatic at the age of scan acquisition (MMSE = 20.6 vs 21.2, p-val ns; CDR global p-val 0.001).

Surprisingly, sEOAD had higher neocortical PiB uptake than DIAD subjects (mean ± SD SUVr = 1.92 ± 0.29 versus 1.58 ± 0.44, d = 0.96). On a similar note, sEOAD had more severe hypometabolism than DIAD participants (mean ± SD SUVr = 1.32 ± 0.1 versus 1.39 ± 0.19, d = 0.48). Voxel-wise comparisons adjusting for age, sex, MMSE, ApoE ε4, and global binding showed higher PiB uptake in sEOAD vs DIAD in medial/dorsal white matter; and lower uptake in sEOAD vs DIAD in medial occipital, thalami, and basal ganglia. Voxel-wise independent component PiB analyses replicated the patterns seen in fully adjusted voxel-wise SUVr models.

The unexpectedly higher global amyloid load in sEOAD vs DIAD could be explained by differences in study recruitment, or amyloid molecular differences in sporadic vs genetic AD leading to a lack of PiB uptake in dominantly inherited forms of AD. Additionally, the DIAD group comprises several mutations, so it is possible that different mutations lead to different amyloid accumulation patterns.

Extremely interesting paper - worth a read beyond this short summary! Even the supplementary material has interesting info! Congrats to all the authors involved!