Is there a risk of prion-like disease transmission by Alzheimer- or Parkinson-associated protein particles?

Abstract

The misfolding and aggregation of endogenous proteins in the central nervous system is a neuropathological hallmark of Alzheimer’s disease (AD), Parkinson’s disease (PD), as well as prion diseases. A molecular mechanism referred to as “nucleation-dependent aggregation” is thought to underlie this neuropathological phenomenon. According to this concept, disease-associated protein particles act as nuclei, or seeds, that recruit cellular proteins and incorporate them, in a misfolded form, into their growing aggregate structure. Experimental studies have shown that the aggregation of the AD-associated proteins amyloid-β (Aβ) and tau, and of the PD-associated protein α-synuclein, can be stimulated in laboratory animal models by intracerebral (i.c.) injection of inocula containing aggregated species of the respective proteins. This has raised the question of whether AD or PD can be transmitted, like certain human prion diseases, between individuals by self-propagating protein particles potentially present on medical instruments or in blood or blood products. While the i.c. injection of inocula containing AD- or PD-associated protein aggregates was found to cause neuronal damage and clinical abnormalities (e.g., motor impairments) in some animal models, none of the studies published so far provided evidence for a transmission of severe or even fatal disease. In addition, available epidemiological data do not indicate a transmissibility of AD or PD between humans. The findings published so far on the effects of experimentally transmitted AD- or PD-associated protein seeds do not suggest specific precautionary measures in the context of hemotherapy, but call for vigilance in transfusion medicine and other medical areas.

Evidence from spatial pattern analysis for the anatomical spread of α-synuclein pathology in Parkinson’s disease dementia

“…across the basolateral amygdala and in the CG and EC [17] and in dentate gyrus granule cells and EC ('perforant path') [6]. The data suggest a close relationship in PDD between the developing pathology and anatomical pathways which could have resulted from the spread of pathogenic α-synuclein in PDD [14,18,35]. This raises the possibility, first proposed by Braak et al [21], that a pathogenic agent introduced via ingestion or inhalation, may transfer along axons to basal areas of the brain, the brain stem, and then to the cerebral cortex.…”

Potential Pathways of Abnormal Tau and α-Synuclein Dissemination in Sporadic Alzheimer's and Parkinson's Diseases

“…However, we prefer to use the term "prion-like" to differentiate sporadic AD and PD from rapidly progressive and infectious prion diseases, as PD and AD have not been shown to be rapidly progressive and contagious (Olanow and McNaught 2011;Iba 2013;Irwin et al 2013;Kaufman and Diamond 2013;Beekes et al 2014;Goedert et al 2014Goedert et al , 2015Brandel et al 2015;Walker and Jucker 2015;Walsh and Selkoe 2016). Available evidence from experimental studies performed in animal and in vitro models indicates that misfolded tau and a-synuclein proteins fulfill the criteria of prionlike proteins, that is to say, seeding/templating, propagation ("spreading"), and structurally differentiated conformations or conformers ("strains") (Aguzzi 2009;Clavaguera et al 2013b;Guo and Lee 2011;Bousset et al 2013;Watts et al 2013;Sanders et al 2014;Melki 2015; Peelaerts et al 2015;Smethurst et al 2015;Woerman et al 2015;Tuttle et al 2016; but see also Bernis et al 2015;Prusiner et al 2015;Supattapone 2015).…”

The link between laughing death and Alzheimer's disease

“…In the meantime, thorough decontamination of surgical instruments and other medical devices remains prudent. 15 Researchers are only starting to appreciate the pathological, diagnostic and therapeutic significance of misfolded proteins. There is no doubt that such advances are urgently needed.…”