Home
The Department of Biomedicine

BBB Seminar: Patrik Brundin - Cancelled!

Is Parkinson’s disease a “prion-like” disorder?

-> Cancelled due to closed airspace <-

 

Patrik Brundin,
Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Sweden

In Parkinson’s disease (PD), aggregates of alpha-synuclein in the cytoplasm and neurites are classical neuropathological findings. These aggregates are called Lewy neurites and Lewy bodies, and are prominent in the substantia nigra where the dopaminergic neurons that suffer the most substantial degeneration in PD are located. Importantly, they are also found in widespread areas throughout the nervous system. According to a hypothesis put forward by Braak and coworkers, the Lewy pathology starts in the olfactory bulb and the dorsal motor nucleus of the vagal nerve and then spreads throughout the nervous system according to a stereotypic pattern, along well-defined anatomical tracts (1).

I will review several recent papers describing that alpha-synuclein aggregates appear in pigmented (i.e. catecholaminergic) embryonic neurons over one decade after they have been grafted (2-5). These aggregates display several of the classical features of Lewy bodies, including Thioflavin S staining, fibril appearance on electron micrographs and immunoreactivity for alpha-synuclein that is phosphorylated at serine residue 129. The frequency of pigmented neurons that exhibited Lewy bodies was 2% in a graft that was 12 years old at the time of the patient’s death and 5% in another implant in the same patient that was 16 years old when the patient died (5). Other grafted cells that did not necessarily display Lewy bodies exhibited signs associated with aging (e.g. increased cytoplasmic staining for alpha-synuclein) (2) and partial functional impairment (e.g. reduced levels of DAT) (4). These changes do not imply that the grafts completely cease to function. Indeed, some patients continue to show transplant-induced improvement well beyond one decade after surgery. Finally, I will briefly touch upon possible mechanisms underlying the transfer of pathology to the young grafted neurons and whether they are relevant to our understanding also of how neuropathology spreads in the non-grafted PD brain (6, 7).

References:

1.  Braak and Del Tredici (2009) Neuroanatomy and pathology of sporadic Parkinson's disease. Adv Anat Embryol Cell Biol 201: 1-119

2.  Li et al (2008) Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 14: 501-3

3.  Kordower et al (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 14: 504-6

4.  Kordower et al (2008) Transplanted dopaminergic neurons develop PD pathologic changes: a second case report. Mov Disord 23: 2303-6

5.  Li et al (2010) Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov Disord [Epub ahead of print]

6.  Brundin et al (2008) Research in motion: the enigma of Parkinson's disease pathology spread. Nat Rev Neurosci 9: 741-5

7.  Brundin et al (2010) Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol 11: 301-7
 

Host: Hans-Hermann Gerdes, Department of Biomedicine