APOE4 and Brain Glucose Metabolism


Given that APOE4 is related to Alzheimer’s Disease, I undertook a search for papers in medline using the search term “apoe4 glucose metabolism brain” which returned 100 papers from 1995-2017. Amongst these papers is the one described below.

Nielsen and colleagues have published an MRI study investigating brain metabolism in APOE4 carriers. The researchers compared APOE3 with APOE4. They used MRI to investigate grey matter volume and PET to investigate cerebral metabolism. They undertook a primary analysis of brain volume/cerebral metabolism correlates with APOE4/APOE3 ratios and also an exploratory analysis. They also corrected for multiple comparisons.

Amongst the key findings

(1) APOE4/APOE3 ratio was  negatively correlated with right hippocampus glucose metabolism

(2) APOE4/APOE3 ratio was negatively correlated with poster cingulate volume after correction

There were a few points about this.

(1) Firstly it is slightly odd that the right hippocampus should be negatively correlated and not the bilateral hippocampi. Could this finding be an artefact or is there an asymmetry in the pathology? These are certainly interesting questions.

(2) Secondly why were the hippocampi unaffected in terms of volumes? Perhaps longitudinal rather than cross-sectional data would help to investigate this.

(3) Thirdly I couldn’t find a reference to the size of the effect. The ratio of APOE4/APOE3 must be a simple number without units. However the correlation with both volume and metabolism must have both a size and a number of units and I couldn’t see this. The relationship was stated in terms of the statistical significance.

There were a number of other interesting findings from the paper but i’m just referencing the ones that I found immediately relevant in terms of the Dual Pathway hypothesis.

The question about asymmetry is I think one of the keys to interpreting these results.


Nielsen HM, Chen K, Lee W, et al. Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism. Alzheimer’s Research & Therapy. 2017;9:5. doi:10.1186/s13195-016-0231-9.

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