Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE epsilon 3/epsilon 3 Subjects

Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E e4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with noncarriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 e3/e3 carriers; 28 e4 carriers) aged 49–79 yr. Leukocyte telomere length correlated inversely with left (rs =20.465; p = 0.011), right (rs =20.414; p = 0.025), and total hippocampus volume (rs =20.519; p = 0.004) among APOE e3/e3 carriers, but not among e4 carriers. However, the e4 carriers fit with the general correlation pattern exhibited by the e3/e3 carriers, as e4 carriers on average had longer telomeres and smaller hippocampi compared with e3/e3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain. Citation: Wikgren M, Karlsson T, Lind J, Nilbrink T, Hultdin J, et al. (2012) Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE e3/e3 Subjects. PLoS ONE 7(4): e34292. doi:10.1371/journal.pone.0034292 Editor: Monica Uddin, Wayne State University, United States of America Received July 15, 2011; Accepted February 25, 2012; Published April 10, 2012 Copyright: 2012 Wikgren et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The research was funded by the Swedish Research Council (grants 2006-4472; 2009-5269; 2009-3413), the Medical Faculty, Umeå University and the County Councils of Västerbotten and Norrbotten, Sweden. The Betula Study is supported by grants 345-2003-3883 and 315-2004-6977 from the Swedish Research Council. The Apolipoprotein E genotyping was funded by the Fund for Scientific Research – Flanders (FWO-V). K.S. holds a postdoctoral fellowship of the FWO-V. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]