Thalamus not basal forebrain is atrophied in non-demented PSEN1 E280A carriers

A previous study of non-demented presenilin-1 (PSEN1) E280A carriers found basal forebrain and hippocampus, but not the thalamus, to be preserved. This study tested the hypothesis of preservation in an independent PSEN1 E280A sample and explored associations with amyloid and tau pathology.

We analyzed multimodal neuroimaging data from 57 individuals in the Colombia-Boston (COLBOS) cohort (non-carriers: 30 and carriers: 27). We used Bayesian multiple regression with priors to test our hypothesis.

Carrier status had no effect on basal forebrain (Bayes factor [BF₁₀] = 0.54) and hippocampal volume (BF₁₀ = 1.05). However, smaller volumes were found in the thalamus of mutation carriers (BF₁₀ = 8.74). We found evidence against an effect of amyloid and tau pathology on basal forebrain, but evidence for an effect on the thalamus.

Our results support the preservation of the cholinergic basal forebrain and hippocampus, while highlighting early thalamic involvement in PSEN1 E280A carriers. This has implications for future selection of treatment targets.

Basal forebrain volume preserved in non-demented presenilin-1 (PSEN1) E280A carriers.Hippocampal volume preserved in non-demented PSEN1 E280A carriers.Thalamic atrophy observed in non-demented PSEN1 E280A carriers.No link between amyloid/tau pathology and basal forebrain volume.Tau burden linked to hippocampal and thalamic volume loss.