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TOMM40 poly-T Variants and Cerebrospinal Fluid Amyloid Beta Levels in the Elderly

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Abstract

A variable poly-T polymorphism in the TOMM40 gene, which is in linkage disequilibrium with APOE, was recently implicated with increased risk and earlier onset age for late-onset Alzheimer’s disease in APOE ε3 carriers. To elucidate potential neurobiological mechanisms underlying this association, we compared the effect of TOMM40 poly-T variants to the effect of APOE, an established LOAD-risk modulator, on cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels, in cognitively intact elderly subjects. APOE ε4 carriers showed significant reductions in Aβ 1-42 levels compared to non-ε4 carriers, but no differences were detected across TOMM40 variants. Neither Aβ 1-40 nor tau levels were affected by APOE or TOMM40.

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Acknowledgments

This study was supported in part by an NIHM Grant (R01 MH080405) to NP. The authors report no conflict of interest. We wish to thank Drs Michael W. Lutz, Ann M. Saunders and Allen D. Roses, Deane Drug Discovery Institute and Department of Medicine, Duke University, Durham, NC, for helping with the preparation of this manuscript and for supervising the TOMM40 polymorphic assays determination.

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Authors and Affiliations

  1. Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Bldg. 35, Orangeburg, NY, 10962, USA

    Nunzio Pomara, Davide Bruno, Jay J. Nierenberg & John J. Sidtis

  2. New York University School of Medicine, New York, NY, USA

    Nunzio Pomara, Davide Bruno, Jay J. Nierenberg, John J. Sidtis & Frank T. Martiniuk

  3. NYS Institute for Basic Research, Staten Island, NY, USA

    Pankaj D. Mehta

  4. Neurochemistry Lab, Sahlgrenska University Hospital, Gothenburg, Sweden

    Henrik Zetterberg & Kaj Blennow

Authors
  1. Nunzio Pomara
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  2. Davide Bruno
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  3. Jay J. Nierenberg
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  4. John J. Sidtis
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  5. Frank T. Martiniuk
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  6. Pankaj D. Mehta
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  7. Henrik Zetterberg
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  8. Kaj Blennow
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Correspondence to Nunzio Pomara.

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Pomara, N., Bruno, D., Nierenberg, J.J. et al. TOMM40 poly-T Variants and Cerebrospinal Fluid Amyloid Beta Levels in the Elderly. Neurochem Res 36, 1124–1128 (2011). https://doi.org/10.1007/s11064-011-0459-5

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  • DOI: https://doi.org/10.1007/s11064-011-0459-5

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