Structural Analysis of Human Brain from Parkinson's Disease Patients

  • Parkinson's disease affects about 1% of us. In most cases, the disease manifests itself at advanced age.

  • In Parkinson's disease, a central region of the human brain, called Substantia nigra, is loosing its typical black pigmented area.

  • Friedrich Lewy identified so-called "Lewy bodies", which are plaques in specific regions of the brain of affected Parkinson patients.

  • Lewy bodies can be found by light microscopy in tiny samples of the brain of Parkinson patients.

  • A widely accepted hypothesis states that specific proteins such as alpha-Synuclein (aSyn) can cluster in needle-like arrays, which in a domino-like "prionoid" effect lets other aSyn proteins adhere. These formed fibrils then cause the plaques in the brain.

  • We use advanced electron microscopes (left) to study human brain samples donated by patients suffering from Parkinson's disease (cartoon on the right). This is a collaboration with Dr. Wilma van de Berg, VUMC, Amsterdam, and scientists at Hoffmann La-Roche, Ltd..

Visualizing neurodeneration by Tokuyasu imaging

About-+

In Parkinson’s disease (PD), degeneration of key brain structures has been linked to the presence of cytoplasmic intraneuronal inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs). In order to characterize the ultrastructure of LBs in brains of PD patients, we have established an analytical workflow of cutting-edge electron microscopy approaches combined with complementary techniques. Our 2-D and 3-D imaging data reveal ultrastructural details previously not known for LBs/LNs. Furthermore, these results are successfully validated using orthogonal methodologies within a multi-disciplinary, cross-institutional team setting. Our new insights on the major compositional structures of LBs within well-preserved postmortem PD human brain tissue are critical to understand disease progression in PD and to design the most appropriate therapeutic strategies.

More detail+-

Lewy bodies occur in a large number of disorders including Alzheimer's disease, Downs syndrome and Picks disease. They are a classic hallmark of Parkinson's disease, where they are primarily found within neurons of the Substaitia Nigra.They are only ocassionally ocurr extracellularly.

There are two types. As shown by electron microscopy, one  .......