Presymptomatic and Symptomatic Stages of Intracerebral Inclusion Body Pathology in Idiopathic Parkinson’s Disease

  • Heiko Braak
  • Kelly Del Tredici


The pathological process that underlies idiopathic Parkinson’s disease (IPD) progresses relentlessly and requires years to reach its full extent, provided it is not terminated prematurely by death. The severity of the pathology increases gradually during the course of the disorder (1, 2, 3, 4, 5, 6, 7, 8). As such, the lesions develop already, to a mild or moderate degree, even in the nervous system of persons whose clinical protocols fail to note the onset or presence of classical IPD-associated motor symptoms (9, 10, 11, 12, 13, 14, 15, 16, 17). Thus, the course of the disease process can be subdivided into presymptomatic and symptomatic phases (Fig. 1A). (3, 5) Like the tip of an iceberg, it is only the symptomatic, later phase of the larger degenerative process that presently can be detected clinically.

Fig. 1. (A)

Presymptomatic and symptomatic phases of idiopathic Parkinson’s disease (IPD). The presymptomatic phase of the disorder is characterized by the appearance of IPD-associated lesions in the brain of asymptomatic persons. Individuals first become symptomatic when the neuropathological threshold is exceeded (approximated by the white vertical line). Increasing density of the shading in areas underneath the diagonal indicates the growing severity of the pathology in vulnerable key regions indicated at the right-hand margin. Arabic numerals mark the stages of the neuropathological process. (B-D) Schematic diagrams showing the gradual ascent of the pathological process underlying IPD (white arrows). (E) Selective vulnerability and resistance of specific neuronal types to IPD. Projection cells that generate long and thin axons are among the nerve cell types most vulnerable to the pathology, whereas projection cells and local circuit neurons with short axon resist the lesions. Heavy axonal myelination offers the following advantages: high speed of conduction, low energy expenditure, greater stability of the parent neuron. Resistant against IPD-related pathology are long-axoned and sturdily myelinated projection neurons. In contrast, vulnerable neuronal types give off unmyelinated or poorly myelinated and thin axons. Reproduced from ref. 6 with permission from Steinkopff Verlag.


Ventral Striatum Vagal Nerve Dorsal Striatum Anterior Thalamic Nucleus Pedunculopontine Nucleus 
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Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Heiko Braak
    • 1
  • Kelly Del Tredici
    • 1
  1. 1.Institute for Clinical NeuroanatomyJ. W. Goethe UniversityFrankfurt/MainGermany

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