Journal of Neural Transmission

, Volume 103, Issue 4, pp 455–490

Pattern of brain destruction in Parkinson's and Alzheimer's diseases

  • H. Braak
  • E. Braak
  • D. Yilmazer
  • R. A. I. de Vos
  • E. N. H. Jansen
  • J. Bohl
Alzheimer's Disease and Related Disorders


Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities which gradually develop in only a small number of neuronal types. In AD, susceptible neurons produce neurofibrillary tangles (NFTs) and neuropil threads (NTs), while in PD, they develop Lewy bodies (LBs) and Lewy neurites (LNs). The specific lesional pattern of both illnesses accrues slowly over time and remains remarkably consistent across cases.

In AD, six developmental stages can be distinguished on account of the predictable manner in which the neurofibrillary changes spread across the cerebral cortex. The pathologic process commences in the transentorhinal region (clinically silent stages I and II), then proceeds into adjoining cortical and subcortical components of the limbic system (stages III and IV — incipient AD), and eventually extends into association areas of the neocortex (stages V and VI — fully developed AD).

During the course of PD, important components of the limbic system undergo specific lesions as well. The predilection sites include the entorhinal region, the CA2-sector of the hippocampal formation, the limbic nuclei of the thalamus, anterior cingulate areas, agranular insular cortex (layer VI), and — within the amygdala — the accessory cortical nucleus, the ventromedial divisions both of the basal and accessory basal nuclei, and the central nucleus. The amygdala not only generates important projections to the prefrental association areas but also exerts influence upon all non-thalamic nuclei which in a non-specific manner project upon the cerebral cortex and upon the nuclei regulating endocrine and autonomie functions. All these amygdala-dependent structures themselves exhibit severe PD-specific lesions. In general, the extranigral destructions are in themselves not sufficient to produce overt intellectual deterioration. Similarly, AD-related pathology up to stage III may be asymptomatic as well. Fully developed PD with concurring incipient AD, however, is likely to cause impaired cognition. Presently available data support the view that the occurrence of additional lesions in the form of AD stage III (or more) destruction is the most common cause of intellectual decline in PD.


Alzheimer's disease Parkinson's disease limbic system neurofibrillary changes Lewy bodies Lewy neurite 


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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. Braak
    • 1
  • E. Braak
    • 1
  • D. Yilmazer
    • 1
  • R. A. I. de Vos
    • 2
  • E. N. H. Jansen
    • 2
  • J. Bohl
    • 3
  1. 1.Zentrum der MorphologieJ.W. Goethe UniversitätFrankfurt/MainFederal Republic of Germany
  2. 2.Streeklaboratoria voor pathologieBurg. Edo bergsmalaanEnschedeThe Netherlands
  3. 3.Abteilung für NeuropathologieJ. Gutenberg UniversitätMainzFederal Republic of Germany

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