Article

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

Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA.
Acta Neuropathologica (Impact Factor: 10.76). 12/2008; 117(2):169-74. DOI: 10.1007/s00401-008-0450-7
Source: PubMed

ABSTRACT Involvement of the olfactory bulb by Lewy-type alpha-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 alpha-synuclein staining of the olfactory bulb in 328 deceased individuals. All cases had received an initial neuropathological examination that included alpha-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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Available from: Charles L White, Aug 21, 2015
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    • "Synucleins comprise a family of small proteins (14–17 kd) that were first identified in normal and neoplastic brain tissues (Fung et al., 2003; George, 2002). It is well established that ␣-synuclein is a key component of the Lewy body, a large globular protein complex that plays a critical role in the pathogenesis of Parkinson's disease (PD) and other dementias known as synucleinopathies (Beach et al., 2009; Bendor et al., 2013). The function of ␣-synuclein in the hematopoietic system is largely unknown. "
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    • "Anatomical pathways Clinical symptoms References Olfactory Bulbs Olfactory impairment Tofaris et al. (2006), Fleming et al. (2008), Lerner and Bagic (2008), Beach et al. (2009), Jellinger (2009), Parkkinen et al. (2009) "
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    • "We reported recently that the Ser129-phosphorylated a-syn deposits were prominently found in the OB of patients with Lewy body-related a-synucleinopathy, while the a-syn rarely co-localized with TH-positive DA cells (Sengoku et al. 2008). Another group reported that a-syn pathology in OB correlated with that in other brain regions in patients with Lewy body-related a-synucleinopathy (Beach et al. 2009). Furthermore, olfactory deficits in the presence of proteinase K-resistant a-syn inclusions were demonstrated in human asyn-transgenic mice (Fleming et al. 2008). "
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