Pathology associated with sporadic Parkinson’s disease — where does it end?
Parkinson’s disease (PD) is a multisystem disorder in which predisposed neuronal types in specific regions of the human peripheral, enteric, and central nervous systems become progressively involved. A staging procedure for the PD-related inclusion body pathology (i.e., Lewy neurites and Lewy bodies) in the brain proposes that the pathological process begins at two sites and progresses in a topographically predictable sequence in 6 stages. During stages 1–2, the inclusion body pathology remains confined to the medulla oblongata, pontine tegmentum, and anterior olfactory structures. In stages 3–4, the basal mid- and forebrain become the focus of the pathology and the illness reaches its symptomatic phase. In the final stages 5–6, the pathological process is seen in the association areas and primary fields of the neocortex. To date, we have staged a total of 301 autopsy cases, including 106 cases with incidental pathology and 176 clinically diagnosed PD cases. In addition, 163 age-matched controls were examined. 19 of the 301 cases with PD-related pathology displayed a pathological distribution pattern of Lewy neurites and Lewy bodies that diverged from the staging scheme described above. In these cases, olfactory structures and the amygdala were predominantly involved in the virtual absence of brain stem pathology. Most of the divergent cases (17/19) had advanced concomitant Alzheimer’s disease-related neurofibrillary changes (stages IV-VI).
Unable to display preview. Download preview PDF.
- Braak H (1980) Architectonics of the human telencephalic cortex. Springer, Berlin Heidelberg, pp 1–147Google Scholar
- Braak H, Braak E, Yilmazer D, Schultz C, Bohl J (1995) Age-related changes of the human cerebral cortex. In: Cruz-Sanchez FF, Ravid R, Cuzner ML (eds) Neuropathological diagnostic criteria for brain banking. IOS Press, Amsterdam, pp 14–19 (Biomedical Health Research, vol 10)Google Scholar
- Brooks DJ (2000) Morphological and functional imaging studies on the diagnosis and progression of Parkinson’s disease. J Neurol 247[Suppl 2]:11–18Google Scholar
- Del Tredici K, Braak H (2004) Idiopathic Parkinson’s disease: staging an α-synucleinopathy with a predictable pathoanatomy. In: Kahle P, Haass C (eds) Molecular mechanisms in Parkinson’s disease. Landes Bioscience, Georgetown, TX, pp 1–32Google Scholar
- Dickson DW (1998) Aging in the central nervous system. In: Markesbery WR (ed) Neuropathology of dementing disorders. Arnold, London New York, pp 56–88Google Scholar
- Hawkes CH, Shephard BC, Daniel SE (1999) Is Parkinson’s disease a primary olfactory disorder? Q J Med 92: 473–480Google Scholar
- Hopkins DA, Bieger D, de Vente J, Steinbusch HWM (1996) Vagal efferent projections: viscerotopy, neurochemistry and effects of vagotomy. Progr Brain Res 107: 79–96Google Scholar
- Jellinger KA, Mizuno Y (2003) Parkinson’s disease. In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 159–187Google Scholar
- Lantos PL, Quinn N (2003) Multiple sytem atrophy. In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 203–214Google Scholar
- Lowe J (1994) Lewy bodies. In: Calne DP (ed) Neurodegenerative diseases. Saunders, Philadelphia, pp 51–69Google Scholar
- Pankratz N, Foroud T (2004) Genetics of Parkinson disease. Neurotox 2: 235–242Google Scholar
- Thal DR, Del Tredici K, Braak H (2004) Neurodegeneration in normal brain aging and disease. Sci Aging Knowledge Environ 23: 1–13Google Scholar
- Wolters EC, Francot C, Bergmans P, Winogrodzka A, Booij J, Berendse HW, Stoof JC (2000) Preclinical (premotor) Parkinson’s disease. J Neurol 247[Suppl 2]: 103–109Google Scholar