Skip to main content
Top
Published in: Clinical Autonomic Research 6/2019

01-12-2019 | Hypotension | Research Article

Association of innervation-adjusted alpha-synuclein in arrector pili muscles with cardiac noradrenergic deficiency in autonomic synucleinopathies

Authors: Risa Isonaka, Christopher H. Gibbons, Ningshan Wang, Roy Freeman, David S. Goldstein

Published in: Clinical Autonomic Research | Issue 6/2019

Login to get access

Abstract

Background

Autonomic synucleinopathies feature deposition of the protein alpha-synuclein (AS) in neurons [e.g., Lewy body neurogenic orthostatic hypotension (nOH)] or glial cells (multiple system atrophy, MSA). AS in skin biopsies might provide biomarkers of these diseases; however, this approach would be complicated or invalidated if there were substantial loss of AS-containing nerves. We report AS content in arrector pili muscles in skin biopsies after adjustment for local innervation in patients with Lewy body nOH or MSA. Cardiac sympathetic neuroimaging by myocardial 18F-dopamine positron emission tomography (PET) was done to examine pathophysiological correlates of innervation-adjusted AS.

Methods

Thirty-one patients (19 Lewy body nOH, 12 MSA) underwent thoracic 18F-dopamine PET and skin biopsies. AS signal intensity analyzed by immunofluorescence microscopy was adjusted for innervation by the ratio of AS to protein gene product (PGP) 9.5, a pan-axonal marker (Harvard lab site), or the ratio of AS to tyrosine hydroxylase (TH), an indicator of catecholaminergic neurons (NIH lab site).

Results

The Lewy body nOH group had higher ratios of AS/PGP 9.5 or log AS/TH than did the MSA group (0.89 ± 0.05 vs. 0.66 ± 0.04, −0.13 ± 0.05 vs. −1.60 ± 0.33; p < 0.00001 each). All 19 Lewy body patients had AS/PGP 9.5 > 0.8 or log AS/TH > 1.2 and had myocardial 18F-dopamine-derived radioactivity < 6000 nCi-kg/cc-mCi, the lower limit of normal. Two MSA patients (17%) had increased AS/PGP or log AS/TH, and two (17%) had low 18F-dopamine-derived radioactivity.

Conclusions

Lewy body forms of nOH are associated with increased innervation-adjusted AS in arrector pili muscles and neuroimaging evidence of myocardial noradrenergic deficiency.
Literature
1.
go back to reference Amino T, Orimo S, Takahashi A, Uchihara T, Mizusawa H (2005) Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Path. 15:29–34 Amino T, Orimo S, Takahashi A, Uchihara T, Mizusawa H (2005) Profound cardiac sympathetic denervation occurs in Parkinson disease. Brain Path. 15:29–34
2.
go back to reference Antelmi E, Donadio V, Incensi A, Plazzi G, Liguori R (2017) Skin nerve phosphorylated α-synuclein deposits in idiopathic REM sleep behavior disorder. Neurology 88:2128–2131PubMed Antelmi E, Donadio V, Incensi A, Plazzi G, Liguori R (2017) Skin nerve phosphorylated α-synuclein deposits in idiopathic REM sleep behavior disorder. Neurology 88:2128–2131PubMed
3.
go back to reference Constantinescu R, Richard I, Kurlan R (2007) Levodopa responsiveness in disorders with parkinsonism: a review of the literature. Mov Disord 22:2141–2148 (quiz 2295) PubMed Constantinescu R, Richard I, Kurlan R (2007) Levodopa responsiveness in disorders with parkinsonism: a review of the literature. Mov Disord 22:2141–2148 (quiz 2295) PubMed
4.
go back to reference Cook GA, Sullivan P, Holmes C, Goldstein DS (2014) Cardiac sympathetic denervation without Lewy bodies in a case of multiple system atrophy. Parkinsonism Relat Disord 20:926–928PubMedPubMedCentral Cook GA, Sullivan P, Holmes C, Goldstein DS (2014) Cardiac sympathetic denervation without Lewy bodies in a case of multiple system atrophy. Parkinsonism Relat Disord 20:926–928PubMedPubMedCentral
5.
go back to reference Delic V, Chandra S, Abdelmotilib H, Maltbie T, Wang S, Kem D, Scott HJ, Underwood RN, Liu Z, Volpicelli-Daley LA, West AB (2018) Sensitivity and specificity of phospho-Ser129 α-synuclein monoclonal antibodies. J Comp Neurol 526:1978–1990PubMedPubMedCentral Delic V, Chandra S, Abdelmotilib H, Maltbie T, Wang S, Kem D, Scott HJ, Underwood RN, Liu Z, Volpicelli-Daley LA, West AB (2018) Sensitivity and specificity of phospho-Ser129 α-synuclein monoclonal antibodies. J Comp Neurol 526:1978–1990PubMedPubMedCentral
6.
go back to reference Donadio V, Cortelli P, Elam M, Di Stasi V, Montagna P, Holmberg B, Giannoccaro MP, Bugiardini E, Avoni P, Baruzzi A, Liguori R (2010) Autonomic innervation in multiple system atrophy and pure autonomic failure. J Neurol Neurosurg Psychiatry 81:1327–1335PubMed Donadio V, Cortelli P, Elam M, Di Stasi V, Montagna P, Holmberg B, Giannoccaro MP, Bugiardini E, Avoni P, Baruzzi A, Liguori R (2010) Autonomic innervation in multiple system atrophy and pure autonomic failure. J Neurol Neurosurg Psychiatry 81:1327–1335PubMed
7.
go back to reference Donadio V, Incensi A, El-Agnaf O, Rizzo G, Vaikath N, Del Sorbo F, Scaglione C, Capellari S, Elia A, Stanzani Maserati M, Pantieri R, Liguori R (2018) Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study. Sci Rep 8:14246PubMedPubMedCentral Donadio V, Incensi A, El-Agnaf O, Rizzo G, Vaikath N, Del Sorbo F, Scaglione C, Capellari S, Elia A, Stanzani Maserati M, Pantieri R, Liguori R (2018) Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study. Sci Rep 8:14246PubMedPubMedCentral
8.
go back to reference Donadio V, Incensi A, Piccinini C, Cortelli P, Giannoccaro MP, Baruzzi A, Liguori R (2016) Skin nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease. Ann Neurol 79:306–316PubMed Donadio V, Incensi A, Piccinini C, Cortelli P, Giannoccaro MP, Baruzzi A, Liguori R (2016) Skin nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease. Ann Neurol 79:306–316PubMed
9.
go back to reference Doppler K, Weis J, Karl K, Ebert S, Ebentheuer J, Trenkwalder C, Klebe S, Volkmann J, Sommer C (2015) Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy. Mov Disord 30:1688–1692PubMed Doppler K, Weis J, Karl K, Ebert S, Ebentheuer J, Trenkwalder C, Klebe S, Volkmann J, Sommer C (2015) Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy. Mov Disord 30:1688–1692PubMed
10.
go back to reference Gibbons CH, Garcia J, Wang N, Shih LC, Freeman R (2016) The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease. Neurology 87:505–512PubMedPubMedCentral Gibbons CH, Garcia J, Wang N, Shih LC, Freeman R (2016) The diagnostic discrimination of cutaneous α-synuclein deposition in Parkinson disease. Neurology 87:505–512PubMedPubMedCentral
11.
go back to reference Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Kockgether T, Lang A, Lantos P, Litvan I, Mathias C, Oliver E, Robertson D, Schatz I, Wenning G (1998) Consensus statement on the diagnosis of multiple system atrophy. Clin Auton Res 8:359–362PubMed Gilman S, Low P, Quinn N, Albanese A, Ben-Shlomo Y, Fowler C, Kaufmann H, Kockgether T, Lang A, Lantos P, Litvan I, Mathias C, Oliver E, Robertson D, Schatz I, Wenning G (1998) Consensus statement on the diagnosis of multiple system atrophy. Clin Auton Res 8:359–362PubMed
12.
go back to reference Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676PubMedPubMedCentral Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71:670–676PubMedPubMedCentral
13.
go back to reference Goldstein DS, Cheshire WP (2018) Roles of catechol neurochemistry in autonomic function testing. Clin Auton Res 28:273–288PubMedPubMedCentral Goldstein DS, Cheshire WP (2018) Roles of catechol neurochemistry in autonomic function testing. Clin Auton Res 28:273–288PubMedPubMedCentral
14.
go back to reference Goldstein DS, Cheshire WP Jr (2017) Beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver. Clin Auton Res 27:361–367PubMedPubMedCentral Goldstein DS, Cheshire WP Jr (2017) Beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver. Clin Auton Res 27:361–367PubMedPubMedCentral
15.
go back to reference Goldstein DS, Holmes C, Bentho O, Sato T, Moak J, Sharabi Y, Imrich R, Conant S, Eldadah BA (2008) Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy. Parkinsonism Relat Disord 14:600–607PubMedPubMedCentral Goldstein DS, Holmes C, Bentho O, Sato T, Moak J, Sharabi Y, Imrich R, Conant S, Eldadah BA (2008) Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy. Parkinsonism Relat Disord 14:600–607PubMedPubMedCentral
16.
go back to reference Goldstein DS, Holmes C, Cannon RO 3rd, Eisenhofer G, Kopin IJ (1997) Sympathetic cardioneuropathy in dysautonomias. N Engl J Med 336:696–702PubMed Goldstein DS, Holmes C, Cannon RO 3rd, Eisenhofer G, Kopin IJ (1997) Sympathetic cardioneuropathy in dysautonomias. N Engl J Med 336:696–702PubMed
17.
go back to reference Goldstein DS, Holmes C, Li ST, Bruce S, Metman LV, Cannon RO 3rd (2000) Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 133:338–347PubMed Goldstein DS, Holmes C, Li ST, Bruce S, Metman LV, Cannon RO 3rd (2000) Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 133:338–347PubMed
18.
go back to reference Goldstein DS, Holmes C, Lopez GJ, Wu T, Sharabi Y (2018) Cardiac sympathetic denervation predicts PD in at-risk individuals. Parkinsonism Relat Disord 52:90–93PubMed Goldstein DS, Holmes C, Lopez GJ, Wu T, Sharabi Y (2018) Cardiac sympathetic denervation predicts PD in at-risk individuals. Parkinsonism Relat Disord 52:90–93PubMed
19.
go back to reference Goldstein DS, Holmes C, Sharabi Y, Brentzel S, Eisenhofer G (2003) Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension. Neurology 60:1327–1332PubMed Goldstein DS, Holmes C, Sharabi Y, Brentzel S, Eisenhofer G (2003) Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension. Neurology 60:1327–1332PubMed
20.
go back to reference Goldstein DS, Holmes C, Sharabi Y, Wu T (2015) Survival in synucleinopathies: a prospective cohort study. Neurology 85:1554–1561PubMedPubMedCentral Goldstein DS, Holmes C, Sharabi Y, Wu T (2015) Survival in synucleinopathies: a prospective cohort study. Neurology 85:1554–1561PubMedPubMedCentral
21.
go back to reference Goldstein DS, Holmes C, Sullivan P, Donadio V, Isonaka R, Zhong E, Pourier B, Vernino S, Kopin IJ, Sharabi Y (2017) Autoimmunity-associated autonomic failure with sympathetic denervation. Clin Auton Res 27:57–62PubMed Goldstein DS, Holmes C, Sullivan P, Donadio V, Isonaka R, Zhong E, Pourier B, Vernino S, Kopin IJ, Sharabi Y (2017) Autoimmunity-associated autonomic failure with sympathetic denervation. Clin Auton Res 27:57–62PubMed
22.
go back to reference Goldstein DS, Polinsky RJ, Garty M, Robertson D, Brown RT, Biaggioni I, Stull R, Kopin IJ (1989) Patterns of plasma levels of catechols in neurogenic orthostatic hypotension. Ann Neurol 26:558–563PubMed Goldstein DS, Polinsky RJ, Garty M, Robertson D, Brown RT, Biaggioni I, Stull R, Kopin IJ (1989) Patterns of plasma levels of catechols in neurogenic orthostatic hypotension. Ann Neurol 26:558–563PubMed
23.
go back to reference Goldstein DS, Sewell L (2009) Olfactory dysfunction in pure autonomic failure: implications for the pathogenesis of Lewy body diseases. Parkinsonism Relat Disord 15:516–520PubMedPubMedCentral Goldstein DS, Sewell L (2009) Olfactory dysfunction in pure autonomic failure: implications for the pathogenesis of Lewy body diseases. Parkinsonism Relat Disord 15:516–520PubMedPubMedCentral
24.
go back to reference Goldstein DS, Sharabi Y (2009) Neurogenic orthostatic hypotension: a pathophysiological approach. Circulation 119:139–146PubMedPubMedCentral Goldstein DS, Sharabi Y (2009) Neurogenic orthostatic hypotension: a pathophysiological approach. Circulation 119:139–146PubMedPubMedCentral
25.
go back to reference Goldstein DS, Sharabi Y (2019) The heart of PD: Lewy body diseases as neurocardiologic disorders. Brain Res 1702:74–84PubMed Goldstein DS, Sharabi Y (2019) The heart of PD: Lewy body diseases as neurocardiologic disorders. Brain Res 1702:74–84PubMed
26.
go back to reference Haga R, Sugimoto K, Nishijima H, Miki Y, Suzuki C, Wakabayashi K, Baba M, Yagihashi S, Tomiyama M (2015) Clinical utility of skin biopsy in differentiating between Parkinson’s disease and multiple system atrophy. Parkinsons Dis 2015:167038PubMedPubMedCentral Haga R, Sugimoto K, Nishijima H, Miki Y, Suzuki C, Wakabayashi K, Baba M, Yagihashi S, Tomiyama M (2015) Clinical utility of skin biopsy in differentiating between Parkinson’s disease and multiple system atrophy. Parkinsons Dis 2015:167038PubMedPubMedCentral
27.
go back to reference Hague K, Lento P, Morgello S, Caro S, Kaufmann H (1997) The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature. Acta Neuropathol 94:192–196PubMed Hague K, Lento P, Morgello S, Caro S, Kaufmann H (1997) The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature. Acta Neuropathol 94:192–196PubMed
28.
go back to reference Ikemura M, Saito Y, Sengoku R, Sakiyama Y, Hatsuta H, Kanemaru K, Sawabe M, Arai T, Ito G, Iwatsubo T, Fukayama M, Murayama S (2008) Lewy body pathology involves cutaneous nerves. J Neuropathol Exp Neurol 67:945–953PubMed Ikemura M, Saito Y, Sengoku R, Sakiyama Y, Hatsuta H, Kanemaru K, Sawabe M, Arai T, Ito G, Iwatsubo T, Fukayama M, Murayama S (2008) Lewy body pathology involves cutaneous nerves. J Neuropathol Exp Neurol 67:945–953PubMed
29.
go back to reference Isonaka R, Holmes C, Cook GA, Sullivan P, Sharabi Y, Goldstein DS (2017) Pure autonomic failure without synucleinopathy. Clin Auton Res 27:97–101PubMed Isonaka R, Holmes C, Cook GA, Sullivan P, Sharabi Y, Goldstein DS (2017) Pure autonomic failure without synucleinopathy. Clin Auton Res 27:97–101PubMed
30.
go back to reference Isonaka R, Rosenberg AZ, Sullivan P, Corrales A, Holmes C, Sharabi Y, Goldstein DS (2019) Alpha-synuclein deposition within sympathetic noradrenergic neurons is associated with myocardial noradrenergic deficiency in neurogenic orthostatic hypotension. Hypertension 73:910–918PubMed Isonaka R, Rosenberg AZ, Sullivan P, Corrales A, Holmes C, Sharabi Y, Goldstein DS (2019) Alpha-synuclein deposition within sympathetic noradrenergic neurons is associated with myocardial noradrenergic deficiency in neurogenic orthostatic hypotension. Hypertension 73:910–918PubMed
31.
go back to reference Isonaka R, Sullivan P, Jinsmaa Y, Corrales A, Goldstein DS (2018) Spectrum of abnormalities of sympathetic tyrosine hydroxylase and alpha-synuclein in chronic autonomic failure. Clin Auton Res 28:223–230PubMed Isonaka R, Sullivan P, Jinsmaa Y, Corrales A, Goldstein DS (2018) Spectrum of abnormalities of sympathetic tyrosine hydroxylase and alpha-synuclein in chronic autonomic failure. Clin Auton Res 28:223–230PubMed
32.
go back to reference Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, Goldstein DS, Peltier AC, Shibao CA, Gibbons CH, Freeman R, Robertson D (2017) Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol 81:287–297PubMedPubMedCentral Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, Goldstein DS, Peltier AC, Shibao CA, Gibbons CH, Freeman R, Robertson D (2017) Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol 81:287–297PubMedPubMedCentral
33.
go back to reference McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O’Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M, Kosaka K (2017) Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89:88–100PubMedPubMedCentral McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O’Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M, Kosaka K (2017) Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89:88–100PubMedPubMedCentral
34.
go back to reference McShane RH, Nagy Z, Esiri MM, King E, Joachim C, Sullivan N, Smith AD (2001) Anosmia in dementia is associated with Lewy bodies rather than Alzheimer’s pathology. J Neurol Neurosurg Psychiatry 70:739–743PubMedPubMedCentral McShane RH, Nagy Z, Esiri MM, King E, Joachim C, Sullivan N, Smith AD (2001) Anosmia in dementia is associated with Lewy bodies rather than Alzheimer’s pathology. J Neurol Neurosurg Psychiatry 70:739–743PubMedPubMedCentral
35.
go back to reference Melli G, Vacchi E, Biemmi V, Galati S, Staedler C, Ambrosini R, Kaelin-Lang A (2018) Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease. Ann Clin Transl Neurol 5:1394–1407PubMedPubMedCentral Melli G, Vacchi E, Biemmi V, Galati S, Staedler C, Ambrosini R, Kaelin-Lang A (2018) Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease. Ann Clin Transl Neurol 5:1394–1407PubMedPubMedCentral
36.
go back to reference Orimo S, Amino T, Takahashi A, Kojo T, Uchihara T, Mori F, Wakabayashi K, Takahashi H (2006) Cardiac sympathetic denervation in Lewy body disease. Parkinsonism Relat Disord 12(Suppl 2):S99–S105 Orimo S, Amino T, Takahashi A, Kojo T, Uchihara T, Mori F, Wakabayashi K, Takahashi H (2006) Cardiac sympathetic denervation in Lewy body disease. Parkinsonism Relat Disord 12(Suppl 2):S99–S105
37.
go back to reference Orimo S, Kanazawa T, Nakamura A, Uchihara T, Mori F, Kakita A, Wakabayashi K, Takahashi H (2007) Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy. Acta Neuropathol 113:81–86PubMed Orimo S, Kanazawa T, Nakamura A, Uchihara T, Mori F, Kakita A, Wakabayashi K, Takahashi H (2007) Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy. Acta Neuropathol 113:81–86PubMed
38.
go back to reference Orimo S, Ozawa E, Oka T, Nakade S, Tsuchiya K, Yoshimoto M, Wakabayashi K, Takahashi H (2001) Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA. Neurology 57:1140–1141PubMed Orimo S, Ozawa E, Oka T, Nakade S, Tsuchiya K, Yoshimoto M, Wakabayashi K, Takahashi H (2001) Different histopathology accounting for a decrease in myocardial MIBG uptake in PD and MSA. Neurology 57:1140–1141PubMed
39.
go back to reference Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100PubMed Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79–100PubMed
40.
go back to reference Raffel DM, Koeppe RA, Little R, Wang CN, Liu S, Junck L, Heumann M, Gilman S (2006) PET measurement of cardiac and nigrostriatal denervation in parkinsonian syndromes. J Nucl Med 47:1769–1777PubMed Raffel DM, Koeppe RA, Little R, Wang CN, Liu S, Junck L, Heumann M, Gilman S (2006) PET measurement of cardiac and nigrostriatal denervation in parkinsonian syndromes. J Nucl Med 47:1769–1777PubMed
41.
go back to reference Shishido T, Ikemura M, Obi T, Yamazaki K, Terada T, Sugiura A, Saito Y, Murayama S, Mizoguchi K (2010) alpha-synuclein accumulation in skin nerve fibers revealed by skin biopsy in pure autonomic failure. Neurology 74:608–610PubMed Shishido T, Ikemura M, Obi T, Yamazaki K, Terada T, Sugiura A, Saito Y, Murayama S, Mizoguchi K (2010) alpha-synuclein accumulation in skin nerve fibers revealed by skin biopsy in pure autonomic failure. Neurology 74:608–610PubMed
42.
go back to reference Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840PubMed Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840PubMed
43.
go back to reference Stankovic I, Quinn N, Vignatelli L, Antonini A, Berg D, Coon E, Cortelli P, Fanciulli A, Ferreira JJ, Freeman R, Halliday G, Hoglinger GU, Iodice V, Kaufmann H, Klockgether T, Kostic V, Krismer F, Lang A, Levin J, Low P, Mathias C, Meissner WG, Kaufmann LN, Palma JA, Panicker JN, Pellecchia MT, Sakakibara R, Schmahmann J, Scholz SW, Singer W, Stamelou M, Tolosa E, Tsuji S, Seppi K, Poewe W, Wenning GK (2019) A critique of the second consensus criteria for multiple system atrophy. Mov Disord Stankovic I, Quinn N, Vignatelli L, Antonini A, Berg D, Coon E, Cortelli P, Fanciulli A, Ferreira JJ, Freeman R, Halliday G, Hoglinger GU, Iodice V, Kaufmann H, Klockgether T, Kostic V, Krismer F, Lang A, Levin J, Low P, Mathias C, Meissner WG, Kaufmann LN, Palma JA, Panicker JN, Pellecchia MT, Sakakibara R, Schmahmann J, Scholz SW, Singer W, Stamelou M, Tolosa E, Tsuji S, Seppi K, Poewe W, Wenning GK (2019) A critique of the second consensus criteria for multiple system atrophy. Mov Disord
44.
go back to reference Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249:180–182PubMed Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett 249:180–182PubMed
45.
go back to reference Wang N, Gibbons CH, Freeman R (2011) Novel immunohistochemical techniques using discrete signal amplification systems for human cutaneous peripheral nerve fiber imaging. J Histochem Cytochem 59:382–390PubMedPubMedCentral Wang N, Gibbons CH, Freeman R (2011) Novel immunohistochemical techniques using discrete signal amplification systems for human cutaneous peripheral nerve fiber imaging. J Histochem Cytochem 59:382–390PubMedPubMedCentral
46.
47.
go back to reference Zange L, Noack C, Hahn K, Stenzel W, Lipp A (2015) Phosphorylated α-synuclein in skin nerve fibres differentiates Parkinson’s disease from multiple system atrophy. Brain 138:2310–2321PubMed Zange L, Noack C, Hahn K, Stenzel W, Lipp A (2015) Phosphorylated α-synuclein in skin nerve fibres differentiates Parkinson’s disease from multiple system atrophy. Brain 138:2310–2321PubMed
48.
go back to reference Ziegler MG, Lake CR, Kopin IJ (1977) The sympathetic-nervous-system defect in primary orthostatic hypotension. N Engl J Med 296:293–297PubMed Ziegler MG, Lake CR, Kopin IJ (1977) The sympathetic-nervous-system defect in primary orthostatic hypotension. N Engl J Med 296:293–297PubMed
Metadata
Title
Association of innervation-adjusted alpha-synuclein in arrector pili muscles with cardiac noradrenergic deficiency in autonomic synucleinopathies
Authors
Risa Isonaka
Christopher H. Gibbons
Ningshan Wang
Roy Freeman
David S. Goldstein
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
Clinical Autonomic Research / Issue 6/2019
Print ISSN: 0959-9851
Electronic ISSN: 1619-1560
DOI
https://doi.org/10.1007/s10286-019-00644-6

Other articles of this Issue 6/2019

Clinical Autonomic Research 6/2019 Go to the issue