Background: Mutations of the PSEN1 gene are linked to the early onset of dementia. Post mortem studies have revealed increased amyloid deposition within the brains of these subjects. The distribution of amyloid appears to be distinct from sporadic AD (SAD).

We aim to investigate a range of pre-symptomatic and mildly affected mutation carriers to confirm the presence of amyloid and to identify patterns of deposition that may be distinctive to PSEN1.

Method: Seven mutation carriers (5 cognitively normal and 2 mildly affected (MMSE≥20)), 10 SAD and 10 healthy controls were studied. 11C-PiB-PET was performed on all subjects. All PET images were co-registered to T1-weighted MRIs and regions of interest were generated using an in-house atlas. Pontine ratios were generated of the following regions: anterior and posterior cingulated, thalamus, striatum and the frontal, temporal, parietal occipital and cerebellar cortices.

Results: SAD subjects had significantly higher 11C-PIB binding compared to controls and PSEN1 carriers. PSEN1 carriers had significantly higher levels of 11C-PIB binding when compared to controls. Two patterns of amyloid distribution emerged. Firstly, emphasis on the striatum occurring in E184D and intron 4 mutations and secondly, increased cerebellar and thalamic uptake in M1461 and Y115C mutations.

Conclusions: PSEN1 gene carriers represent a distinctive group of patients. To date 185 mutations of PSEN1 gene have been published. In this study we have demonstrated the importance of investigating a range of PSEN1 mutations as different patterns of amyloid deposition have emerged. We also confirmed the presence of amyloid in the cerebellum of these subjects supporting the use of the pons as the reference region for this cohort.