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
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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, Oct 04, 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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    ABSTRACT: α-synuclein plays a crucial role in Parkinson's disease and dementias defined as synucleinopathies. α-synuclein is expressed in hematopoietic and immune cells, but its functions in hematopoiesis and immune responses are unknown. We utilized α-synuclein-/− (KO) mice to investigate its role in hematopoiesis and B cell lymphopoiesis. We demonstrated hematologic abnormalities including mild anemia, smaller platelets, lymphopenia but relatively normal early hematopoiesis in KO mice compared to wild-type (WT) as measured in hematopoietic stem cells and progenitors of the different cell lineages. However, the absolute number of B220+IgM+ B cells in bone marrow was reduced by 4-fold in KO mice (WT: 104 ± 23 × 105 vs. KO: 27 ± 5 × 105). B cells were also reduced in KO spleens associated with effacement of splenic and lymph node architecture. KO mice showed reduced total serum IgG but no abnormality in serum IgM was noted. When KO mice were challenged with a T cell-dependent antigen, production of antigen specific IgG1 and IgG2b was abolished, but antigen specific IgM was not different from WT mice. Our study shows hematologic abnormalities including anemia and smaller platelets, reduced B cell lymphopoiesis and defects in IgG production in the absence of α-synuclein. This is the first report to show an important role of α-synuclein late in hematopoiesis, B cell lymphopoiesis and adaptive immune response
    Immunobiology 11/2014; 219(11). DOI:10.1016/j.imbio.2014.07.014 · 3.04 Impact Factor
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    • "Firstly, from a pathophysiological perspective, they may be caused by different mechanisms. hyposmia in PD was associated with alpha-synuclein accumulation in central olfactory system, especially the olfactory bulb [12,13]. Whereas, SN hyperechogenicity may reflect increased SN iron content in PD, this was demonstrated in animal models and postmortem human brains [14,15]. "
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    ABSTRACT: Objectives Both hyposmia and substania nigra (SN) hyperechogenicity on trascranial sonography (TCS) were risk markers for idiopathic Parkinson’s disease (PD), which was beneficial to the differential diagnosis of the disease. However, each of their single diagnostic value is often limited. The purpose of present study was to explore whether the combination of olfactory test and TCS of SN could enhance the differential diagnostic power in Chinese patients with PD. Methods Thirty-seven patients with PD and twenty-six patients with essential tremor (ET) were evaluated on 16-item odor identification test from extended version of sniffin’ sticks and TCS of SN. The frequency of hyposmia and SN hyperechogenicity in each group was compared. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the two clinical biomarkers were analyzed. Results The frequency of hyposmia in patients with PD was significantly higher than in patients with ET (62.2% VS. 3.8%, P = 0.000). The frequency of SN hyperechogenicity in patients with PD was significantly higher than in ET subjects (48.6% VS. 15.4%, P = 0.006). The combination of hyposmia and SN hyperechogenicity (if either one or both present) discriminated patients with PD from ET with a sensitivity of 78.4% and 29.7%, specificity of 80.8% and 100%, PPV of 85.3% and 100%, and NPV of 72.4% and 50.0%, respectively. Conclusions Our preliminary data suggested that the combination of hyposmia and SN hyperechogenicity could improve the diagnostic potential for discriminating Chinese patients with PD from ET.
    Translational Neurodegeneration 12/2012; 1(1):25. DOI:10.1186/2047-9158-1-25
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    • "In addition to reduced odor identification prior to the onset of PD, olfactory dysfunction also has been frequently recognized in patients with ILBD [31]. Also, neuropathological olfactory bulb alpha-synclein has high specificity and sensitivity for Lewy body formation in confirmed cases of PD and DLB [32]. On the basis of pathological studies of a large number of autopsy cases, Braak et al. proposed a hypothesis as to the onset and advancement pattern of PD in that the disease developed from the medulla and olfactory bulb and extended to the pons and substantia nigra (SN) [33]. "
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    ABSTRACT: Objectives. Both results of the odor identification and cardiac (123)I-metaiodobenzylguanidine accumulation have been investigated for their potential to enhance the detection of pathogenesis resembling that of Lewy body-related α-synucleinopathies in patients clinically diagnosed as having idiopathic REM sleep behavior disorder. Methods. We performed both the Odor Stick Identification Test for Japanese and (123)I-metaiodobenzylguanidine scintigraphy in 30 patients with idiopathic REM sleep behavior disorder, 38 patients with Parkinson's disease, and 20 control subjects. Results. In idiopathic REM sleep behavior disorder, reduced odor identification score and an early or delayed heart to mediastinum ratio on (123)I-metaiodobenzylguanidine were almost as severe as in Parkinson's disease patients. Delayed cardiac (123)I-metaiodobenzylguanidine uptake was even more severe in the idiopathic REM sleep behavior disorder group than in the Parkinson's disease group. Conclusions. Reduced cardiac (123)I-metaiodobenzylguanidine uptake, which is independent of parkinsonism, may be more closely associated with idiopathic REM sleep behavior disorder than olfactory impairment.
    04/2011; 2011:941268. DOI:10.4061/2011/941268
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