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Olfactory bulb α-synucleinopathy has high specificity and sensitivity for Lewy body disorders

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Abstract

Involvement of the olfactory bulb by Lewy-type α-synucleinopathy (LTS) is known to occur at an early stage of Parkinson’s disease (PD) and Lewy body disorders and is therefore of potential usefulness diagnostically. An accurate estimate of the specificity and sensitivity of this change has not previously been available. We performed immunohistochemical α-synuclein staining of the olfactory bulb in 328 deceased individuals. All cases had received an initial neuropathological examination that included α-synuclein immunohistochemical staining on sections from brainstem, limbic and neocortical regions, but excluded olfactory bulb. These cases had been classified based on their clinical characteristics and brain regional distribution and density of LTS, as PD, dementia with Lewy bodies (DLB), Alzheimer’s disease with LTS (ADLS), Alzheimer’s disease without LTS (ADNLS), incidental Lewy body disease (ILBD) and elderly control subjects. The numbers of cases found to be positive and negative, respectively, for olfactory bulb LTS were: PD 55/3; DLB 34/1; ADLS 37/5; ADNLS 19/84; ILBD 14/7; elderly control subjects 5/64. The sensitivities and specificities were, respectively: 95 and 91% for PD versus elderly control; 97 and 91% for DLB versus elderly control; 88 and 91% for ADLS versus elderly control; 88 and 81% for ADLS versus ADNLS; 67 and 91% for ILBD versus elderly control. Olfactory bulb synucleinopathy density scores correlated significantly with synucleinopathy scores in all other brain regions (Spearman R values between 0.46 and 0.78) as well as with scores on the Mini-Mental State Examination and Part 3 of the Unified Parkinson’s Disease Rating Scale (Spearman R −0.27, 0.35, respectively). It is concluded that olfactory bulb LTS accurately predicts the presence of LTS in other brain regions. It is suggested that olfactory bulb biopsy be considered to confirm the diagnosis in PD subjects being assessed for surgical therapy.

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Acknowledgments

We wish to acknowledge all of the other members of the Arizona Parkinson’s Disease Consortium, including John Caviness MD, Virgilio Evidente MD, Erika Driver-Dunckley MD, Padma Mahant MD, and Johan Samanta MD. This research is supported by grants to the Sun Health Research Institute Brain Donation Program and the Arizona Parkinson’s Disease Consortium by the Michael J. Fox Foundation for Parkinson’s Research (The Prescott Family Initiative), the Arizona Biomedical Research Commission (contracts 4001, 0011 and 05-901) and the National Institute on Aging (P30 AG19610).

Conflict of interest statement

All authors have declared that they have no competing interests.

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Authors and Affiliations

  1. Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA

    Thomas G. Beach, Marwan N. Sabbagh, Donald J. Connor, Holly A. Shill, Lucia I. Sue, Jeanne Sasse, Jyothi Bachalakuri & Jonette Henry-Watson

  2. University of Texas Southwestern Medical Center, Dallas, TX, USA

    Charles L. White III & Christa L. Hladik

  3. Tokyo Institute of Psychiatry, Tokyo, Japan

    Haru Akiyama

  4. Mayo Clinic, Scottsdale, AZ, USA

    Charles H. Adler

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  1. Thomas G. Beach
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Correspondence to Thomas G. Beach.

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Beach, T.G., White, C.L., Hladik, C.L. et al. Olfactory bulb α-synucleinopathy has high specificity and sensitivity for Lewy body disorders. Acta Neuropathol 117, 169–174 (2009). https://doi.org/10.1007/s00401-008-0450-7

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  • DOI: https://doi.org/10.1007/s00401-008-0450-7

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