Cited by 1,021Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

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Parkinson's disease: a dual‐hit hypothesis

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Hawkes, C. H., Del Tredici, K., Braak, H.·2007·Neuropathology and Applied Neurobiology

DOI 10.1111/j.1365-2990.2007.00874.xPMC PMC7194308

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Abstract

Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non-motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose - hence the term 'dual-hit'.

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Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777
Self-citation
The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.
Gibb, W. R., & Lees, A. J. (1988) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.51.6.745 · Cited by 3,481
Diagnostic Criteria for Parkinson Disease
Gelb, D. J., Oliver, E., & Gilman, S. (1999) · Archives of Neurology · doi:10.1001/archneur.56.1.33 · Cited by 2,822
Stages in the development of Parkinson’s disease-related pathology
Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., & Del Tredici, K. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0956-9 · Cited by 2,689
Self-citation
‘Sniffin’ Sticks': Olfactory Performance Assessed by the Combined Testing of Odour Identification, Odor Discrimination and Olfactory Threshold
Hummel, T., Sekinger, B., Wolf, S. R., Pauli, E., & Kobal, G. (1997) · Chemical Senses · doi:10.1093/chemse/22.1.39 · Cited by 2,501
Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen
Braak, H., R�b, U., Gai, W. P., & Del Tredici, K. (2003) · Journal of Neural Transmission · doi:10.1007/s00702-002-0808-2 · Cited by 1,683
Self-citation
The human nervous system
Paxinos, G., & Jürgen, K. (2004) · Cited by 1,478
Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology
Braak, H., de Vos, R. A. I., Bohl, J., & Del Tredici, K. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.11.012 · Cited by 1,354
Self-citation
Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder
Schenck, C. H., Bundlie, S. R., & Mahowald, M. W. (1996) · Neurology · doi:10.1212/wnl.46.2.388 · Cited by 1,083
SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders
Litvan, I., Bhatia, K. P., Burn, D. J., Goetz, C. G., Lang, A. E., McKeith, I. G., Quinn, N. P., Sethi, K. D., Shults, C. W., & Wenning, G. K. (2003) · Movement Disorders · doi:10.1002/mds.10459 · Cited by 1,011
Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease.
Pearson, R. C., Esiri, M. M., Hiorns, R. W., Wilcock, G. K., & Powell, T. P. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.13.4531 · Cited by 987
Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease
Boeve, B. F., Silber, M. H., Saper, C. B., Ferman, T. J., Dickson, D. W., Parisi, J. E., Benarroch, E. E., Ahlskog, J. E., Smith, G. E., Caselli, R., et al. (2007) · Brain · doi:10.1093/brain/awm056 · Cited by 986
Self-citation
Gastrointestinal dysfunction in Parkinson's disease
Pfeiffer, R. F. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00307-7 · Cited by 933
Types of neurons in the enteric nervous system
Furness, J. B. (2000) · Journal of the Autonomic Nervous System · doi:10.1016/s0165-1838(00)00127-2 · Cited by 855
Assessment of autonomic dysfunction in Parkinson's disease: The SCOPA‐AUT
Jeukens‐Visser, M., Marinus, J., Stiggelbout, A. M., & van Hilten, J. J. (2004) · Movement Disorders · doi:10.1002/mds.20153 · Cited by 841
Frequency of Bowel Movements and the Future Risk of Parkinson’s Disease
Abbott, R. D., Petrovitch, H., White, L. R., Masaki, K. H., Tanner, C. M., Curb, J. D., Grandinetti, A., Blanchette, P. L., Popper, J. S., & Ross, G. W. (2001) · Neurology · doi:10.1212/wnl.57.3.456 · Cited by 839
Olfactory dysfunction in parkinsonism: A general deficit unrelated to neurologic signs, disease stage, or disease duration
Doty, R. L., Deems, D. A., & Stellar, S. (1988) · Neurology · doi:10.1212/wnl.38.8.1237 · Cited by 838
Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease
Hughes, A. J., Daniel, S. E., & Lees, A. J. (2001) · Neurology · doi:10.1212/wnl.57.8.1497 · Cited by 807
Where Does Parkinson Disease Pathology Begin in the Brain?
Del Tredici, K., Rüb, U., de Vos, R. A. I., Bohl, J. R. E., & Braak, H. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.5.413 · Cited by 773
Self-citation
Idiopathic hyposmia as a preclinical sign of Parkinson's disease
Ponsen, M. M., Stoffers, D., Booij, J., van Eck‐Smit, B. L. F., Wolters, E. C., & Berendse, H. W. (2004) · Annals of Neurology · doi:10.1002/ana.20160 · Cited by 758
Association of olfactory dysfunction with risk for future Parkinson's disease
Ross, G. W., Petrovitch, H., Abbott, R. D., Tanner, C. M., Popper, J. S., Masaki, K., Launer, L. J., & White, L. R. (2007) · Annals of Neurology · doi:10.1002/ana.21291 · Cited by 739
Development of the 12‐Item Cross‐Cultural Smell Identification Test(CC‐SIT)
Doty, R. L., Marcus, A., & Lee, W. W. (1996) · The Laryngoscope · doi:10.1097/00005537-199603000-00021 · Cited by 734
Pathology of Parkinson’s disease
Jellinger, K. A. (1991) · Molecular and Chemical Neuropathology · doi:10.1007/bf03159935 · Cited by 708
The parkinson's complex: Parkinsonism is just the tip of the iceberg
Langston, J. W. (2006) · Annals of Neurology · doi:10.1002/ana.20834 · Cited by 608
Entry of peroxidase into neurons of the central and peripheral nervous systems from extracerebral and cerebral blood
Broadwell, R. D., & Brightman, M. (1976) · The Journal of Comparative Neurology · doi:10.1002/cne.901660302 · Cited by 519
Neurodegenerative Diseases
(1994) · Toxicology and Industrial Health · doi:10.1177/074823379401000603 · Cited by 501
Lewy bodies
Shults, C. W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509567103 · Cited by 495
Excessive daytime sleepiness and subsequent development of Parkinson disease
Abbott, R. D., Ross, G. W., White, L. R., Tanner, C. M., Masaki, K., Nelson, J. S., Curb, J. D., & Petrovitch, H. (2005) · Neurology · doi:10.1212/01.wnl.0000183056.89590.0d · Cited by 439
Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for -synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT
Stiasny‐Kolster, K. (2004) · Brain · doi:10.1093/brain/awh322 · Cited by 430
Progression of Dysarthria and Dysphagia in Postmortem-Confirmed Parkinsonian Disorders
Müller, J., Wenning, G. K., Verny, M., McKee, A. C., Chaudhuri, К. R., Jellinger, K. A., Poewe, W. H., & Litvan, I. (2001) · Archives of Neurology · doi:10.1001/archneur.58.2.259 · Cited by 426
Neuropathology of Autonomic Nervous System in Parkinson's Disease
Wakabayashi, K., & Takahashi, H. (2008) · European Neurology · doi:10.1159/000113469 · Cited by 407
Olfactory dysfunction in Parkinson's disease.
Hawkes, C. H., Shephard, B. C., & Daniel, S. E. (1997) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.62.5.436 · Cited by 399
Self-citation
Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder
Postuma, R. B., Lang, A. E., Massicotte-Marquez, J., & Montplaisir, J. Y. (2006) · Neurology · doi:10.1212/01.wnl.0000203648.80727.5b · Cited by 392
Olfactory function in patients with Parkinson's disease
Ansari, K. A., & Johnson, A. (1975) · Journal of Chronic Diseases · doi:10.1016/0021-9681(75)90058-2 · Cited by 375
Cardiac Sympathetic Denervation in Parkinson Disease
Goldstein, D. S., Holmes, C., Li, S.-T., Bruce, S., Metman, L. V., & Cannon, R. O. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-133-5-200009050-00009 · Cited by 372
Anatomy and physiology of the enteric nervous system
Costa, M., Brookes, S., & Hennig, G. (2000) · Gut · doi:10.1136/gut.47.suppl_4.iv15 · Cited by 364
Alzheimer Disease With Amygdala Lewy Bodies: A Distinct Form of α-Synucleinopathy
Uchikado, H., Lin, W.-L., DeLucia, M. W., & Dickson, D. W. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000225908.90052.07 · Cited by 359
Challenges in Parkinson's disease: restoration of the nigrostriatal dopamine system is not enough
Lang, A. E., & Obeso, J. A. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00740-9 · Cited by 348
Neuropathological spectrum of synucleinopathies
Jellinger, K. A. (2003) · Movement Disorders · doi:10.1002/mds.10557 · Cited by 345
Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD
Iranzo, Á., Santamaría, J., Rye, D. B., Valldeoriola, F., Martí, M. J., Muñoz, E., Vilaseca, I., & Tolosa, E. (2005) · Neurology · doi:10.1212/01.wnl.0000168864.97813.e0 · Cited by 344
α‐Synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects
Bloch, A., Probst, A., Bissig, H., Adams, H., & Tolnay, M. (2006) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00727.x · Cited by 337
Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson's disease.
Doty, R. L., Stern, M. B., Pfeiffer, C., Gollomp, S. M., & Hurtig, H. I. (1992) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.55.2.138 · Cited by 329
α‐Synuclein pathology does not predict extrapyramidal symptoms or dementia
Parkkinen, L., Kauppinen, T., Pirttilä, T., Autere, J. M., & Alafuzoff, I. I. (2004) · Annals of Neurology · doi:10.1002/ana.20321 · Cited by 328
Parkinson’s disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons
Braak, H., Sastre, M., Böhl, J., de Vos, R. A. I., & Tredici, K. D. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0193-x · Cited by 325
Self-citation
Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system
Wakabayashi, K., Takahashi, H., Ohama, E., & Ikuta, F. (1990) · Acta Neuropathologica · doi:10.1007/bf00294234 · Cited by 324
A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in Parkinson's disease
Huisman, E., Uylings, H. B. M., & Hoogland, P. V. J. M. (2004) · Movement Disorders · doi:10.1002/mds.10713 · Cited by 314
Esophageal Lewy bodies associated with ganglion cell loss in achalasia
Qualman, S. J., Haupt, H. M., Yang, P. H., & Hamilton, S. R. (1984) · Gastroenterology · doi:10.1016/0016-5085(84)90079-9 · Cited by 305
Amygdala pathology in Parkinson's disease
Braak, H., Braak, E., Yilmazer‐Hanke, D., de Vos, R. A. I., Jansen, E. N. H., Böhl, J., & Jellinger, K. A. (1994) · Acta Neuropathologica · doi:10.1007/bf00296485 · Cited by 297
Self-citation
Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases
Mufson, E. J., Kroin, J. S., Sendera, T. J., & Sobreviela, T. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00059-8 · Cited by 296
Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease.
Qualman, S. J., Haupt, H. M., Yang, P. H., & Hamilton, S. R. (1984) · PubMed · Cited by 295
Olfaction in neurodegenerative disorder
Hawkes, C. H. (2003) · Movement Disorders · doi:10.1002/mds.10379 · Cited by 294
Self-citation
THE DISTRIBUTION OF LEWY BODIES IN THE CENTRAL AND AUTONOMIC NERVOUS SYSTEMS IN IDIOPATHIC PARALYSIS AGITANS
Jager, W. A. D. H., & Bethlem, J. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.4.283 · Cited by 292
The anterior olfactory nucleus in Parkinson's disease
Pearce, R. K. B., Hawkes, C. H., & Daniel, S. E. (1995) · Movement Disorders · doi:10.1002/mds.870100309 · Cited by 289
Self-citation
Lewy body–type degeneration in cardiac plexus in Parkinson’s and incidental Lewy body diseases
Iwanaga, K., Wakabayashi, K., Yoshimoto, M., Tomita, I., Satoh, H., Takashima, H., Satoh, A., Seto, M., Tsujihata, M., & Takahashi, H. (1999) · Neurology · doi:10.1212/wnl.52.6.1269 · Cited by 277
Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease
Orimo, S., Amino, T., Itoh, Y., Takahashi, A., Kojo, T., Uchihara, T., Tsuchiya, K., Mori, F., Wakabayashi, K., & Takahashi, H. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-0995-7 · Cited by 264
Neuropathology of synuclein aggregates
Duda, J. E., Lee, V. M. ‐., & Trojanowski, J. Q. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20000715)61:2 · Cited by 263
Lewy body-related ?-synucleinopathy in the aged human brain
Jellinger, K. A. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0138-7 · Cited by 253
Gastric emptying time and gastric motility in patients with Parkinson's disease
Hardoff, R., Sula, M., Tamir, A., Soil, A., Front, A., Badarna, S., Honigman, S., & Giladi, N. (2001) · Movement Disorders · doi:10.1002/mds.1203 · Cited by 248
Detection of presymptomatic Parkinson's disease: Combining smell tests, transcranial sonography, and SPECT
Sommer, U., Hummel, T. R., Cormann, K., Mueller, A., Frasnelli, J., Kropp, J., & Reichmann, H. (2004) · Movement Disorders · doi:10.1002/mds.20141 · Cited by 244
Increased Muscle Activity During Rapid Eye Movement Sleep Correlates with Decrease of Striatal Presynaptic Dopamine Transporters. IPT and IBZM SPECT Imaging in Subclinical and Clinically Manifest Idiopathic REM Sleep Behavior Disorder, Parkinson's Disease, and Controls
Eisensehr, I., Linke, R., Tatsch, K., Kharraz, B., Gildehaus, J. F., Wetter, C. T., Trenkwalder, C., Schwarz, J., & Noachtar, S. (2003) · SLEEP · doi:10.1093/sleep/26.5.507 · Cited by 239
Axonal and transneuronal transport in the transmission of neurological disease: Potential role in system degenerations, including alzheimer's disease
Saper, C., Wainer, B. H., & German, D. C. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90063-7 · Cited by 239
Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies
Kaufmann, H., Nahm, K., Purohit, D. P., & WOLFE, D. E. (2004) · Neurology · doi:10.1212/01.wnl.0000138500.73671.dc · Cited by 239
Gastrointestinal dysfunction in Parkinson's disease
Edwards, L., Quigley, E., & Pfeiffer, R. (1992) · Neurology · doi:10.1212/wnl.42.4.726 · Cited by 226
Chemical coding of the human gastrointestinal nervous system: Cholinergic, VIPergic, and catecholaminergic phenotypes
Anlauf, M., Schäfer, M. K.-H., Eiden, L. E., & Weihe, E. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10599 · Cited by 213
The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature
Hague, K., Lento, P., Morgello, S., Caro, S., & Kaufmann, H. (1997) · Acta Neuropathologica · doi:10.1007/s004010050693 · Cited by 209
Transport of molecules from nose to brain: Transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium
Shipley, M. T. (1985) · Brain Research Bulletin · doi:10.1016/0361-9230(85)90129-7 · Cited by 208
Cardiac sympathetic denervation from the early stage of Parkinson's disease: clinical and experimental studies with radiolabeled MIBG.
Takatsu, H., Nishida, H., Matsuo, H., Watanabe, S., Nagashima, K., Wada, H., Noda, T., Nishigaki, K., & Fujiwara, H. (2000) · PubMed · Cited by 200
Lewy Body-Related α-Synucleinopathy in Aging
Saito, Y., Ruberu, N. N., Sawabe, M., Arai, T., Kazama, H., Hosoi, T., Yamanouchi, H., & Murayama, S. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.7.742 · Cited by 200
Autonomic dysfunction in Parkinson's disease: a comprehensive symptom survey
Siddiqui, M. F., Rast, S. A., Lynn, M., Auchus, A. P., & Pfeiffer, R. F. (2002) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(01)00052-9 · Cited by 195
Association of olfactory dysfunction with incidental Lewy bodies
Ross, G. W., Abbott, R. D., Petrovitch, H., Tanner, C. M., Davis, D. G., Nelson, J. R., Markesbery, W. R., Hardman, J. M., Masaki, K., Launer, L. J., et al. (2006) · Movement Disorders · doi:10.1002/mds.21076 · Cited by 194
Cerebrospinal fluid antibodies to coronavirus in patients with Parkinson's disease
Fazzini, E., Fleming, J. O., & Fahn, S. (1992) · Movement Disorders · doi:10.1002/mds.870070210 · Cited by 193
Ambulatory ECG and analysis of heart rate variability in Parkinson's disease
Haapaniemi, T. H. (2001) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.70.3.305 · Cited by 193
The Vagus Nerve is One Route of Transneural Invasion for Intranasally Inoculated Influenza A Virus in Mice
Matsuda, K., Park, C. H., Sunden, Y., Kimura, T., Ochiai, K., Kida, H., & Umemura, T. (2004) · Veterinary Pathology · doi:10.1354/vp.41-2-101 · Cited by 189
How to diagnose dementia with Lewy bodies: State of the art
Geser, F., Wenning, G. K., Poewe, W. H., & McKeith, I. G. (2005) · Movement Disorders · doi:10.1002/mds.20535 · Cited by 184
Pathology associated with sporadic Parkinson’s disease — where does it end?
Braak, H., Müller, C. M., Rüb, U., Ackermann, H., Bratzke, H., de Vos, R. A. I., & Tredici, K. D. (2006) · Springer eBooks · doi:10.1007/978-3-211-45295-0_15 · Cited by 182
Self-citation
Olfaction
Doty, R. L. (2001) · Annual Review of Psychology · doi:10.1146/annurev.psych.52.1.423 · Cited by 180
Poor and protracted myelination as a contributory factor to neurodegenerative disorders
Braak, H., & Tredici, K. D. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.04.001 · Cited by 179
Self-citation
The invasion routes of neurovirulent A/Hong Kong/483/97 (H5N1) influenza virus into the central nervous system after respiratory infection in mice
Park, C. H., Ishinaka, M., Takada, A., Kida, H., Kimura, T., Ochiai, K., & Umemura, T. (2002) · Archives of Virology · doi:10.1007/s00705-001-0750-x · Cited by 164
Alpha-Synuclein Lesions in Normal Aging, Parkinson Disease, and Alzheimer Disease: Evidence from the Baltimore Longitudinal Study of Aging (BLSA)
Mikolaenko, I., Pletniková, O., Kawas, C. H., O’Brien, R., Resnick, S. M., Crain, B. J., & Troncoso, J. C. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.156 · Cited by 163
Autonomic dysfunction in Parkinson's disease
Micieli, G., Tosi, P., Marcheselli, S., & Cavallini, A. (2003) · Neurological Sciences · doi:10.1007/s100720300035 · Cited by 157
Olfaction and Parkinson's syndromes: its role in differential diagnosis
Katzenschlager, R., & Lees, A. J. (2004) · Current Opinion in Neurology · doi:10.1097/01.wco.0000137531.76491.c2 · Cited by 157
Lewy bodies in the visceral autonomic nervous system in Parkinson's disease.
Wakabayashi, K., Takahashi, H. E., Ohama, E., Takeda, S., & Ikuta, F. (1993) · PubMed · Cited by 154
Olfactory threshold in Parkinson's disease.
Quinn, N. P., Rossor, M. N., & MARSDEN, C. D. (1987) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.50.1.88 · Cited by 153
Is Parkinson's disease a primary olfactory disorder?
Hawkes, C. H. (1999) · QJM · doi:10.1093/qjmed/92.8.473 · Cited by 152
Self-citation
Neurodegeneration in Normal Brain Aging and Disease
Thal, D. R., Del Tredici, K., & Braak, H. (2004) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2004.23.pe26 · Cited by 149
Self-citation
An experimental study of the ventral striatum of the golden hamster. II. Neuronal connections of the olfactory tubercle
Newman, R. S., & Winans, S. S. (1980) · The Journal of Comparative Neurology · doi:10.1002/cne.901910204 · Cited by 142
Chapter 5 Vagal efferent projections: viscerotopy, neurochemistry and effects of vagotomy
Hopkins, D. A., Bieger, D., de Vente, J., & Steinbusch, H. W. M. (1996) · Progress in brain research · doi:10.1016/s0079-6123(08)61859-2 · Cited by 141
Sleep issues in Parkinson’s disease
Adler, C. H., & Thorpy, M. J. (2005) · Neurology · doi:10.1212/wnl.64.12_suppl_3.s12 · Cited by 139
Loss of 123I-MIBG uptake by the heart in Parkinson's disease: assessment of cardiac sympathetic denervation and diagnostic value.
Satoh, A., Serita, T., Seto, M., Tomita, I., Satoh, H., Iwanaga, K., Takashima, H., & Tsujihata, M. (1999) · PubMed · Cited by 139
Diagnostic staging of Parkinson?s disease: conceptual aspects
Przuntek, H., M�ller, T., & Riederer, P. F. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-003-0102-y · Cited by 137
The Expression of α-, β-, and γ-Synucleins in Olfactory Mucosa from Patients with and without Neurodegenerative Diseases
Duda, J. E., Shah, U., Arnold, S. E., Lee, V. M. ‐., & Trojanowski, J. Q. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7228 · Cited by 133
Chemosensory event-related potentials in response to trigeminal and olfactory stimulation in idiopathic Parkinson's disease
Barz, S., Hummel, T. R., Pauli, E., Majer, M., Lang, C. J. G., & Kobal, G. (1997) · Neurology · doi:10.1212/wnl.49.5.1424 · Cited by 131
Olfactory deficit in idiopathic rapid eye movements sleep behavior disorder
Fantini, M. L., Postuma, R. B., Montplaisir, J. Y., & Ferini‐Strambi, L. (2006) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2006.07.008 · Cited by 130
Significance of123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: It can be a specific marker for Lewy body disease
Taki, J., Yoshita, M., Yamada, M., & Tonami, N. (2004) · Annals of Nuclear Medicine · doi:10.1007/bf02984560 · Cited by 130
Quantitative study of salivary secretion in Parkinson's disease
Tumilasci, O. R., Cersosimo, M. G., Belforte, J. E., Micheli, F. E., Benarroch, E. E., & Pazo, J. H. (2006) · Movement Disorders · doi:10.1002/mds.20784 · Cited by 128
α-Synuclein pathology in the spinal cords of neurologically asymptomatic aged individuals
Klos, K. J., Ahlskog, J. E., Josephs, K. A., Apaydın, H., Parisi, J. E., Boeve, B. F., DeLucia, M. W., & Dickson, D. W. (2006) · Neurology · doi:10.1212/01.wnl.0000204179.88955.fa · Cited by 127
Herpes simplex encephalitis
Tomlinson, A. H., & Esiri, M. M. (1983) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(83)90158-2 · Cited by 126
Preliminary diagnosis of Parkinson's disease by olfactory bulb pathology
Daniel, S. E., & Hawkes, C. (1992) · The Lancet · doi:10.1016/0140-6736(92)93275-r · Cited by 125
Self-citation
Impaired gastric emptying of a solid test meal in patients with Parkinson's disease using 13C-sodium octanoate breath test
Goetze, O., Wieczorek, J., Mueller, T. J., Przuntek, H., Schmidt, W. E., & Woitalla, D. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.11.007 · Cited by 116
Direct spread of reovirus from the intestinal lumen to the central nervous system through vagal autonomic nerve fibers.
Morrison, L. A., Sidman, R. L., & Fields, B. N. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.9.3852 · Cited by 115
Critical appraisal of brain pathology staging related to presymptomatic and symptomatic cases of sporadic Parkinson’s disease
Halliday, G. M., Tredici, K. D., & Braak, H. (2006) · Springer eBooks · doi:10.1007/978-3-211-45295-0_16 · Cited by 113
Self-citation
Immunologic diseases, anti-inflammatory drugs, and Parkinson disease: A case-control study
Bower, J. H., Maraganore, D. M., Peterson, B. J., Ahlskog, J. E., & Rocca, W. A. (2006) · Neurology · doi:10.1212/01.wnl.0000227906.99570.cc · Cited by 113
The cellular pathology of Parkinson's disease
Takahashi, H., & Wakabayashi, K. (2001) · Neuropathology · doi:10.1046/j.1440-1789.2001.00403.x · Cited by 109
The Human Nervous System 2nd ed
Coon, D. (1975) · Physical Therapy · doi:10.1093/ptj/55.9.1034a · Cited by 109
Progressive Postnatal Assembly of Limbic–Autonomic Circuits Revealed by Central Transneuronal Transport of Pseudorabies Virus
Rinaman, L., Levitt, P. R., & Card, J. P. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-07-02731.2000 · Cited by 106
Dorsal motor nucleus of the vagus nerve: A cyto‐ and chemoarchitectonic study in the human
Huang, X., Törk, I., & Paxinos, G. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903300203 · Cited by 95
Staging of Sporadic Parkinson Disease-Related α-Synuclein Pathology: Inter- and Intra-Rater Reliability
Müller, C. M., de Vos, R. A. I., Maurage, C., Thal, D. R., Tolnay, M., & Braak, H. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000171652.40083.15 · Cited by 94
Self-citation
Autonomic dysfunctions in idiopathic Parkinson's disease
Jost, W. H. (2003) · Journal of Neurology · doi:10.1007/s00415-003-1105-z · Cited by 90
Influenza Virus Antigen in Postencephalitic Parkinsonism Brain
Gamboa, E. T. (1974) · Archives of Neurology · doi:10.1001/archneur.1974.00490400042003 · Cited by 89
Abnormal performance on the PD test battery by asymptomatic first-degree relatives
Montgomery, E. B., Baker, K. B., Lyons, K., & Koller, W. C. (1999) · Neurology · doi:10.1212/wnl.52.4.757 · Cited by 89
Challenging conventional wisdom: The etiologic role of dopamine oxidative stress in Parkinson's disease
Ahlskog, J. E. (2004) · Movement Disorders · doi:10.1002/mds.20362 · Cited by 83
Correlation between cardiac 123I‐MIBG and odor identification in patients with Parkinson's disease and multiple system atrophy
Lee, P. H., Yeo, S. H., Kim, H. J., & Youm, H. Y. (2006) · Movement Disorders · doi:10.1002/mds.21083 · Cited by 81
Transneuronal transport of herpes simplex virus from the cervical vagus to brain neurons with axonal inputs to central vagal sensory nuclei in the rat
Blessing, W. W., Li, Y.-W., & Wesselingh, S. L. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90163-i · Cited by 78
Preclinical (premotor) Parkinson’s disease
Wolters, E. C., Francot, C. M. J. E., Bergmans, P., Winogrodzka, A., Booij, J., Berendse, H. W., & Stoof, J. C. (2000) · Journal of Neurology · doi:10.1007/pl00022910 · Cited by 76
The intermediolateral nucleus and Clarke's column in Parkinson's disease
Wakabayashi, K., & Takahashi, H. (1997) · Acta Neuropathologica · doi:10.1007/s004010050705 · Cited by 76
Recent advances in the use of neurotropic viruses for circuit analysis
Enquist, L. W., & Card, J. P. (2003) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2003.08.001 · Cited by 72
Abnormal co-contraction in yips-affected but not unaffected golfers: Evidence for focal dystonia
Adler, C. H., Crews, D. J., Hentz, J. G., Smith, A. M., & Caviness, J. N. (2005) · Neurology · doi:10.1212/01.wnl.0000162024.05514.03 · Cited by 72
Olfactory dysfunction in Guamanian ALS, parkinsonism, and dementia
Ahlskog, J. E., Waring, S. C., Petersen, R. C., Esteban-Santillan, C., Craig, U.-K., O’Brien, P. C., Plevak, M. F., & Kurland, L. T. (1998) · Neurology · doi:10.1212/wnl.51.6.1672 · Cited by 69
Riechprüfung mit "sniffin' sticks" zur klinischen Diagnostik des Morbus Parkinson
Daum, R. F., Sekinger, B., Kobal, G., & Lang, C. J. G. (2000) · Der Nervenarzt · doi:10.1007/s001150050640 · Cited by 68
Regional Distribution of Proteinase K-Resistant α-Synuclein Correlates with Lewy Body Disease Stage
Neumann, M., Müller, V., Kretzschmar, H. A., Haass, C., & Kahle, P. J. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.12.1225 · Cited by 66
Decreased myocardial123I-MIBG uptake in Parkinson's disease
Iwasa, K., Nakajima, K., Yoshikawa, H., Tada, A., Taki, J., & Takamori, M. (1998) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1998.tb05957.x · Cited by 65
Smell identification ability in twin pairs discordant for Parkinson's disease
Marras, C., Goldman, S. M., Smith, A., Barney, P., Aston, D. A., Comyns, K., Korell, M., Langston, J. W., Ross, G. W., & Tanner, C. M. (2005) · Movement Disorders · doi:10.1002/mds.20389 · Cited by 65
Avian influenza virus intranasally inoculated infects the central nervous system of mice through the general visceral afferent nerve
Shinya, K., SHIMADA, A., Ito, T., Otsuki, K., MORITA, T., Tanaka, H., Takada, A., Kida, H., & Umemura, T. (2000) · Archives of Virology · doi:10.1007/s007050050016 · Cited by 64
Chapter 27 The neurobiology of the central nucleus of the amygdala in relation to neuroendocrine and autonomic outflow
Bohus, B., Koolhaas, J. M., Luiten, P. G. M., Korte, S. M., Roozendaal, B., & Wiersma, A. (1996) · Progress in brain research · doi:10.1016/s0079-6123(08)61881-6 · Cited by 64
Targeting of host-cell ubiquitin pathways by viruses
Shackelford, J., & Pagano, J. S. (2005) · Essays in Biochemistry · doi:10.1042/eb0410139 · Cited by 62
Olfaction in Parkinson’s disease: methods of assessment and clinical relevance
Liberini, P., Parola, S., Spano, P., & Antonini, L. (2000) · Journal of Neurology · doi:10.1007/pl00007803 · Cited by 57
Epstein–Barr virus oncogenesis and the ubiquitin–proteasome system
Masucci, M. G. (2004) · Oncogene · doi:10.1038/sj.onc.1207372 · Cited by 51
Pathogenesis and preclinical course of Parkinson’s disease
Foley, P., & Riederer, P. F. (1999) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6360-3_2 · Cited by 50
Ocular pathogenicity of herpes simplex virus
Hill, T. J. (1987) · Current Eye Research · doi:10.3109/02713688709020060 · Cited by 50
Defecatory disorders in de novo Parkinsonians--colonic transit and electromyogram of the external anal sphincter.
Jost, W. H., & Schrank, B. (1998) · PubMed · Cited by 50
Exploring brain circuitry with neurotropic viruses: New horizons in neuroanatomy
Card, J. P. (1998) · The Anatomical Record · doi:10.1002/(sici)1097-0185(199812)253:6 · Cited by 48
Projections from the central nucleus of the amygdala to the gastric related area of the dorsal vagal complex: a Phaseolus vulgaris-leucoagglutinin study in rat
Lyubashina, O. A., Jolkkonen, E., & Pitkänen, A. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01392-6 · Cited by 43
Viral Antibodies in Serum and CSF of Parkinsonian Patients and Controls
Elizan, T. S., Madden, D. L., Noble, G. R., Herrmann, K. L., Gardner, J., Schwartz, J., Smith, H., Sever, J. L., & Yahr, M. D. (1979) · Archives of Neurology · doi:10.1001/archneur.1979.00500450023002 · Cited by 43
Cortical Connections and the Pathology of Alzheimer's Disease
Pearson, R. C. A. (1996) · Neurodegeneration · doi:10.1006/neur.1996.0058 · Cited by 40
A possible role of influenza A virus infection for Parkinson's disease.
Takahashi, M., & Yamada, T. (2001) · PubMed · Cited by 40
Herpesviruses and Parkinsonism
Marttila, R. J. (1981) · Archives of Neurology · doi:10.1001/archneur.1981.00510010045007 · Cited by 38
The Central Nucleus of the Amygdala Modulates Gut‐Related Neurons in the Dorsal Vagal Complex in Rats
Zhang, X., Cui, J., Tan, Z. T., Jiang, C., & Fogel, R. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.045906 · Cited by 37
Search for viral particles and virus‐specific products in idiopathic Parkinson disease brain material
Schwartz, J. L., & Elizan, T. S. (1979) · Annals of Neurology · doi:10.1002/ana.410060314 · Cited by 37
Dysphagia and dementia in subjects with Parkinson's disease
Bine, J. E., Frank, E. M., & McDade, H. L. (1995) · Dysphagia · doi:10.1007/bf00260970 · Cited by 37
[Objective olfactometry: methodological annotations for recording olfactory EEG-responses from the awake human].
Kobal, G., & Plattig, K.-H. (1978) · PubMed · Cited by 37
Nucleic Acid Homology Studies of Viral Nucleic Acids in Idiopathic Parkinson's Disease
Wetmur, J. G., Schwartz, J., & Elizan, T. S. (1979) · Archives of Neurology · doi:10.1001/archneur.1979.00500440032004 · Cited by 35
A Route for Prion Neuroinvasion
Nicotera, P. (2001) · Neuron · doi:10.1016/s0896-6273(01)00385-3 · Cited by 33
Influenza Virus Antibodies in Parkinsonism
Marttila, R. J. (1977) · Archives of Neurology · doi:10.1001/archneur.1977.00500140053010 · Cited by 32
Molecular Mechanisms of Parkinson's Disease
Rezaee, Z., Marandi, M., Alaei, H., & Esfarjani, F. (2019) · The Neuroscience Journal of Shefaye Khatam · doi:10.29252/shefa.8.1.120 · Cited by 30
Virus antibodies in Parkinson's disease
Marttila, R. J., Rinne, U. K., & Tiilikainen, A. S. (1982) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(82)90184-8 · Cited by 29
Controversy: Is Parkinson's disease a single disease entity? Yes
Takahashi, H., & Wakabayashi, K. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2005.02.011 · Cited by 29
Human intermediate reticular zone: A cyto and chemoarchitectonic study
Huang, X., & Paxinos, G. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903600403 · Cited by 28
Lower Brainstem Regulation of Visceral, Cardiovascular, and Respiratory Function
Blessing, W. W., & Benarroch, E. E. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-374236-0.10029-x · Cited by 27
Effect of neonatal nomifensine exposure on adult behavior and brain monoamines in rats
Hilakivi, L. A., Hilakivi, I. T., Ahtee, L., Haikala, H. M., & Attila, M. (1987) · Journal of Neural Transmission · doi:10.1007/bf01252512 · Cited by 23
Colonic Transit Time in Nonidiopathic Parkinson’s Syndrome
Jost, W. H., Jung, G., & Schimrigk, К. (2008) · European Neurology · doi:10.1159/000117072 · Cited by 21
Lower Brain Stem Regulation of Visceral, Cardiovascular, and Respiratory Function
Blessing, W. W. (2004) · Elsevier eBooks · doi:10.1016/b978-012547626-3/50016-8 · Cited by 20
Sorting Signals and Targeting of Infectious Agents Through Axons: An Annotation to the 100 Years' Birth of the Name “Axon”
Kristensson, K. (1996) · Brain Research Bulletin · doi:10.1016/s0361-9230(96)00255-9 · Cited by 19
Palatal myoclonus: An unusual presentation
Ross, S., & Jankovic, J. J. (2005) · Movement Disorders · doi:10.1002/mds.20516 · Cited by 19
Acute parkinsonism in suspected herpes simplex encephalitis
Solbrig, M. V., & Nashef, L. A. M. (1993) · Movement Disorders · doi:10.1002/mds.870080226 · Cited by 18
The viral hypothesis in parkinsonism.
Elizan, T. S., & Casals, J. (1983) · PubMed · Cited by 16
[Sense of smell in allergic rhinitis].
Klimek, L. (1998) · PubMed · Cited by 15
SMELL AND TASTE COMPLAINTS
Lueck, C. J. (2003) · Brain · doi:10.1093/brain/awg097 · Cited by 7
List of Abstracts from the Twenty-eighth Annual Meeting of the Association for Chemoreception Sciences
(2006) · Chemical Senses · doi:10.1093/chemse/bjj055 · Cited by 6
Smell and taste complaints
Hawkes, C. H. (2002) · Butterworth-Heinemann eBooks · Cited by 5
Self-citation
Tic douloureux, Parkinson’s disease and the herpes connection
Howard, J. S. (1997) · Integrative Psychological and Behavioral Science · doi:10.1007/bf02688623 · Cited by 5
Nasal mucosa in patients with Parkinson's disease
Witt, M., Gudziol, V., Haehner, A., Reichmann, H., & Hummel, T. (2006) · doi:10.13140/rg.2.1.2076.3289 · Cited by 5
Untitled work
(2000) · doi:10.1002/1531-8257(200005)15:3
Untitled work
(2001) · doi:10.1002/1531-8257(200101)16:1

Research works printed but not linked: 4

Braak H, 2005, Parkinson's Disease: Progress in Research., 1
Sulla M, 1996, Gastric emptying time and gastric motility in patients with untreated Parkinson's disease, Mov Disord, 11, 1041
Schenck CH, 2003, REM behavior disorder (RBD), delayed emergence of parkinsonism and/or dementia in 65% of older men initially diagnosed with idiopathic RBD, and an analysis of the minimum & maximum tonic and/or phasic electromyographic abnormalities found during REM sleep, Sleep, 26, 316
10.1042/bse0410139 · DOI

Sorted by citations

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See all 1,021

Authors: Hawkes, C. H., Del Tredici, K., & Braak, H.
Affiliations: Queen's Hospital (GB)
Goethe University Frankfurt (DE)
Corresponding author: Hawkes, C. H.
ORCID: Hawkes, C. H.
Braak, H.
Venue: Neuropathology and Applied Neurobiology
Publisher: Wiley
Published: 2007-10-24
Volume: 33
Issue: 6
Pages: 599-614
ISSN: 0305-1846 (ISSN-L)
1365-2990
DOI: 10.1111/j.1365-2990.2007.00874.x
PMC: PMC7194308
OpenAlex: W2105047187
Cited by: 1,021
References: 163
Citations by year: 2026: 35 · 2025: 59 · 2024: 87 · 2023: 82 · 2022: 104 · 2021: 117 · 2020: 83 · 2019: 59 · 2018: 49 · 2017: 63 · 2016: 41 · 2015: 33 · 2014: 32 · 2013: 40 · 2012: 33
FWCI: 2.90
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Neuropathology and Applied Neurobiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Parkinson's disease, neurotropic viruses, olfactory dysfunction, Lewy bodies, vagal dysfunction, sleep disorder, olfactory bulb, submucosal plexus, vagus nerve, substantia nigra, prodromal Parkinson's disease, viral pathogenesis
MeSH terms: Animals, Olfaction Disorders, Gastrointestinal Diseases, Heart Diseases, Humans, Models, Neurological, Parkinson Disease, Sleep Wake Disorders, Virus Diseases

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Parkinson's disease: a dual‐hit hypothesis

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