. Alzheimer Disease Signature Neurodegeneration and APOE Genotype in Mild Cognitive Impairment With Suspected Non-Alzheimer Disease Pathophysiology. JAMA Neurol. 2017 Jun 1;74(6):650-659. PubMed.


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  1. This report by Jagust and colleagues represents an interesting and valuable contribution to the literature on SNAP. They demonstrate that there is little difference when using either hippocampal volume or FDG-PET for classifying neurodegeneration. In line with previous literature, they show that in MCI, those classified as SNAP do not exhibit as pronounced a degenerative trajectory as their Aβ-amyloid/ neurodegeneration positive counterparts (Aβ+N+). However, in a number of evaluations this difference appeared to be moderated by APOE; where the SNAP group contained fewer ε4 carriers and more ε2 carriers. In cognitively normals there were no reported differences between the SNAP and Aβ+N+ except for the prevalence of APOE ε4 and ε2. The results suggest that APOE ε4/ ε2 carriage is a differentiating factor for pronounced/slow degeneration in N+ individuals: whether this is in addition to, or in linkage with, the effect of Aβ positivity is unclear and requires further investigation.

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