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Amyotrophic Lateral Sclerosis/parkinsonism Dementia Complex (amyotrophic + lateral_parkinsonism_dementia_complex)
Selected AbstractsCommentary on: return of the cycad hypothesis , does the amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2006P. A. Cox First page of article [source] Return of the cycad hypothesis , does the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health?NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2005P. G. Ince Recently published work provides evidence in support of the cycad hypothesis for Lytico,Bodig, the Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC), based on a new understanding of Chamorro food practices, a cyanobacterial origin of ,-methylaminoalanine (BMAA) in cycad tissue, and a possible mechanism of biomagnification of this neurotoxic amino acid in the food chain. BMAA is one of two cycad chemicals with known neurotoxic properties (the other is cycasin, a proven developmental neurotoxin) among the many substances that exist in these highly poisonous plants, the seeds of which are used by Chamorros for food and medicine. The traditional diet includes the fruit bat, a species that feeds on cycad seed components and reportedly bioaccumulates BMAA. Plant and animal proteins provide a previously unrecognized reservoir for the slow release of this toxin. BMAA is reported in the brain tissue of Guam patients and early data suggest that some Northern American patients dying of Alzheimer's disease (AD) have detectable brain levels of BMAA. The possible role of cyanobacterial toxicity in sporadic neurodegenerative disease is therefore worthy of consideration. Recent neuropathology studies of ALS/PDC confirm understanding of this disorder as a ,tangle' disease, based on variable anatomical burden, and showing biochemical characteristics of ,AD-like' combined 3R and 4R tau species. This model mirrors the emerging view that other neurodegenerative disease spectra comprise clusters of related syndromes, owing to common molecular pathology, with variable anatomical distribution in the nervous system giving rise to different clinical phenotypes. Evidence for ,ubiquitin-only' inclusions in ALS/PDC is weak. Similarly, although there is evidence for ,-synucleinopathy in ALS/PDC, the parkinsonian component of the disease is not caused by Lewy body disease. The spectrum of sporadic AD includes involvement of the substantia nigra and a high prevalence of ,incidental',-synucleinopathy in sporadic AD is reported. Therefore the pathogenesis of Lytico,Bodig appears still to have most pertinence to the ongoing investigation of the pathogenesis of AD and other tauopathies. [source] Environmental neurotoxin-induced progressive model of parkinsonism in ratsANNALS OF NEUROLOGY, Issue 1 2010Wei-Bin Shen PhD Objective Exposure to a number of drugs, chemicals, or environmental factors can cause parkinsonism. Epidemiologic evidence supports a causal link between the consumption of flour made from the washed seeds of the plant Cycas micronesica by the Chamorro population of Guam and the development of amyotrophic lateral sclerosis/parkinsonism dementia complex. Methods We now report that consumption of washed cycad flour pellets by Sprague-Dawley male rats induces progressive parkinsonism. Results Cycad-fed rats displayed motor abnormalities after 2 to 3 months of feeding such as spontaneous unilateral rotation, shuffling gait, and stereotypy. Histological and biochemical examination of brains from cycad-fed rats revealed an initial decrease in the levels of dopamine and its metabolites in the striatum (STR), followed by neurodegeneration of dopaminergic (DAergic) cell bodies in the substantia nigra (SN) pars compacta (SNc). ,-Synuclein (,-syn; proteinase K-resistant) and ubiquitin aggregates were found in the DAergic neurons of the SNc and neurites in the STR. In addition, we identified ,-syn aggregates in neurons of the locus coeruleus and cingulate cortex. No loss of motor neurons in the spinal cord was found after chronic consumption of cycad flour. In an organotypic slice culture of the rat SN and the striatum, an organic extract of cycad causes a selective loss of dopamine neurons and ,-syn aggregates in the SN. Interpretation Cycad-fed rats exhibit progressive behavioral, biochemical, and histological hallmarks of parkinsonism, coupled with a lack of fatality. ANN NEUROL 2010;68:70,80 [source] | ||||||||||