Montal V, Diez I, Kim CM, Orwig W, Bueichekú E, Gutiérrez-Zúñiga R, Bejanin A, Pegueroles J, Dols-Icardo O, Vannini P, El-Fakhri G, Johnson KA, Sperling RA, Fortea J, Sepulcre J. Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes. Sci Transl Med. 2022 Jul 27;14(655):eabn7273. PubMed.

Recommends

Please login to recommend the paper.

Comments

  1. It is very interesting that APOE expression came up in this study as being associated with the spread of tau pathology. This observation tracks with some recent studies from our group that found reducing APOE levels through antisense oligonucleotides or removal of astrocytic APOE expression reduced tau pathology and tau-dependent neurodegeneration in the P301S tau model.

    The study also brought to mind a very nice recent paper from Oskar Hansson’s group (Vogel et al., 2021) that described  subtypes of tau, one of which, a medial-temporal lobe-sparing form, showed a bias toward APOE4 allele noncarriers. Understanding how APOE genotype, or other genetic factors such as TREM2, influence tau propagation networks will add another layer of nuance.

    The mechanism by which APOE would influence NFT burden is still unclear. As the authors note, interactome studies of NFTs and p-tau protein also identified APOE, raising the question of how and where a secreted, glial-expressed protein like APOE could associate with a predominantly intracellular, neuronal protein like tau. This could happen in the extracellular space or perhaps in autophagic-lysosomal compartments in neurons or glial cells.

    References:

    Vogel JW, Young AL, Oxtoby NP, Smith R, Ossenkoppele R, Strandberg OT, La Joie R, Aksman LM, Grothe MJ, Iturria-Medina Y, Alzheimer’s Disease Neuroimaging Initiative, Pontecorvo MJ, Devous MD, Rabinovici GD, Alexander DC, Lyoo CH, Evans AC, Hansson O. Four distinct trajectories of tau deposition identified in Alzheimer's disease. Nat Med. 2021 May;27(5):871-881. Epub 2021 Apr 29 PubMed.

    View all comments by Jason Ulrich

Make a Comment

To make a comment you must login or register.

This paper appears in the following:

News

  1. Does Tangle Progression Follow ApoE Expression?