Cell and Tissue Research

, Volume 318, Issue 1, pp 121-134

First online:

Stages in the development of Parkinson’s disease-related pathology

  • Heiko BraakAffiliated withInstitute for Clinical Neuroanatomy, J.W. Goethe University Email author 
  • , Estifanos GhebremedhinAffiliated withInstitute for Clinical Neuroanatomy, J.W. Goethe University
  • , Udo RübAffiliated withInstitute for Clinical Neuroanatomy, J.W. Goethe University
  • , Hansjürgen BratzkeAffiliated withInstitute for Forensic Medicine, J.W. Goethe University
  • , Kelly Del TrediciAffiliated withInstitute for Clinical Neuroanatomy, J.W. Goethe University

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The synucleinopathy, idiopathic Parkinson’s disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1–2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3–4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5–6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.


Alpha-synuclein Lewy bodies Lewy neurites Parkinson’s disease Pathoarchitectonics Staging