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Ground zero in Alzheimer's disease

Nature Neuroscience volume 17, pages 146–147 (2014)Cite this article

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New findings in preclinical Alzheimer's disease patients and mouse models of the disease suggest that it is the lateral, rather than the medial, entorhinal cortex that is most susceptible to tau pathology early in Alzheimer's disease. Aberrations begin here and spread to other cortical sites.

Alzheimer's disease robs individuals of their memories and, eventually, all of their cognitive abilities. But where in the brain does it all begin? The entorhinal cortex, a small region in the medial temporal lobe, is a critical component of our episodic memory system1. It is also one of the sites of pathology accumulation and early cellular loss in Alzheimer's disease2,3. In particular, tau abnormalities are noted in this region, and tangle pathology is evident in the entorhinal cortex very early in the course of the disease (Braak stage I)4. However, the entorhinal cortex is not a single homogeneous structure. It is composed of lateral (LEC) and medial (MEC) portions, and different functions have been ascribed to each of these regions5. For example, the LEC is thought to have object processing and nonspatial mnemonic functions5, whereas the MEC, which contains spatially tuned grid cells, is thought to have spatial mnemonic functions6. Past studies have lacked sufficient resolution to examine how these two regions may be differentially targeted by Alzheimer's disease pathology.

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Figure 1: Tau pathology progression in Alzheimer's disease.

Katie Vicari

References

  1. Witter, M.P. Hippocampus 3 (Spec. No), 33–44 (1993).

    PubMed  Google Scholar 

  2. Gómez-Isla, T. et al. J. Neurosci. 16, 4491–4500 (1996).

    Article  Google Scholar 

  3. Van Hoesen, G.W., Hyman, B.T. & Damasio, A.R. Hippocampus 1, 1–8 (1991).

    Article  CAS  Google Scholar 

  4. Braak, H. & Braak, E. Acta Neuropathol. 82, 239–259 (1991).

    Article  CAS  Google Scholar 

  5. Hargreaves, E.L., Rao, G., Lee, I. & Knierim, J.J. Science 308, 1792–1794 (2005).

    Article  CAS  Google Scholar 

  6. Hafting, T., Fyhn, M., Molden, S., Moser, M.-B. & Moser, E.I. Nature 436, 801–806 (2005).

    Article  CAS  Google Scholar 

  7. Khan, U. et al. Nat. Neurosci. 17, 304–311 (2014).

    Article  CAS  Google Scholar 

  8. Palop, J.J. & Mucke, L. Nat. Neurosci. 13, 812–818 (2010).

    Article  CAS  Google Scholar 

  9. Busche, M.A. et al. Science 321, 1686–1689 (2008).

    Article  CAS  Google Scholar 

  10. Sanchez, P.E. et al. Proc. Natl. Acad. Sci. USA 109, E2895–E2903 (2012).

    Article  CAS  Google Scholar 

  11. Bakker, A. et al. Neuron 74, 467–474 (2012).

    Article  CAS  Google Scholar 

  12. Insausti, R., Tuñón, T., Sobreviela, T., Insausti, A.M. & Gonzalo, L.M. J. Comp. Neurol. 355, 171–198 (1995).

    Article  CAS  Google Scholar 

  13. Suzuki, W.A. & Amaral, D.G. J. Comp. Neurol. 350, 497–533 (1994).

    Article  CAS  Google Scholar 

  14. Stranahan, A.M., Haberman, R.P. & Gallagher, M. Cereb. Cortex 21, 392–400 (2011).

    Article  Google Scholar 

Download references

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  1. Michael A. Yassa is in the Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California, USA.,

    Michael A Yassa

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  1. Michael A Yassa
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Correspondence to Michael A Yassa.

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Yassa, M. Ground zero in Alzheimer's disease. Nat Neurosci 17, 146–147 (2014). https://doi.org/10.1038/nn.3631

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