On 14 October, researchers published an article on cerebrospinal fluid (CSF) proteomic associations of APOE genotypes in the Alzheimer’s & Dementia journal. The study examined how different APOE genotypes influence protein patterns in the CSF of individuals at various stages of cognitive function. Using untargeted tandem mass tag mass spectrometry, the researchers analysed CSF samples from 227 cognitively normal controls, 165 cognitively normal amyloid-positive individuals and 177 participants with mild cognitive impairment that were also amyloid positive across two large cohorts. Of the 978 proteins measured, 549 showed differences between APOE ε2/ε3 or ε4 carriers and ε3/ε3 controls.
The ε2/ε3 group displayed higher levels of 280 proteins linked to neuronal plasticity, suggesting potential protective effects. In contrast, ε4 carriers exhibited protein changes associated with blood–brain barrier dysfunction and glucose metabolism, highlighting risk-related mechanisms. By combining data from two cohorts, the researchers were able to characterise the rare ε2 genotype and propose that its protective effects may act through enhanced neuronal plasticity. The article has been published open access and can be read here: