Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders.Their etiologies are idiopathic,and treatments are symptomatic and orientated towards cognitive or motor deficits.Neuropatholog...Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders.Their etiologies are idiopathic,and treatments are symptomatic and orientated towards cognitive or motor deficits.Neuropathologically,both are proteinopathies with pathological aggregates(plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease,and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease).These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages.Both disorders present a long prodromal period,characterized by preclinical signs including hyposmia.Interestingly,the olfactory system,particularly the anterior olfactory nucleus,is initially and preferentially affected by the pathology.Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes.It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding(seeding),which then propagates through neurons and glia(spreading).Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading.Connectomic approaches reveal a number of hubs in the olfactory system(anterior olfactory nucleus,olfactory entorhinal cortex and cortical amygdala)that are key interconnectors with the main hubs(the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus)of network dysfunction in Alzheimer’s and Parkinson’s diseases.展开更多
基金Funding agencies:Sponsored by the Spanish Ministry of Economy and Competitiveness/ERDF(grant no.SAF2016–75768-R)the Autonomous Government of Castilla-La Mancha/ERDF(grant no.SBPLY/17/180501/000430)to AMM.
文摘Alzheimer’s and Parkinson’s diseases are the most prevalent neurodegenerative disorders.Their etiologies are idiopathic,and treatments are symptomatic and orientated towards cognitive or motor deficits.Neuropathologically,both are proteinopathies with pathological aggregates(plaques of amyloid-β peptide and neurofibrillary tangles of tau protein in Alzheimer’s disease,and Lewy bodies mostly composed of α-synuclein in Parkinson’s disease).These deposits appear in the nervous system in a predictable and accumulative sequence with six neuropathological stages.Both disorders present a long prodromal period,characterized by preclinical signs including hyposmia.Interestingly,the olfactory system,particularly the anterior olfactory nucleus,is initially and preferentially affected by the pathology.Cerebral atrophy revealed by magnetic resonance imaging must be complemented by histological analyses to ascertain whether neuronal and/or glial loss or neuropil remodeling are responsible for volumetric changes.It has been proposed that these proteinopathies could act in a prion-like manner in which a misfolded protein would be able to force native proteins into pathogenic folding(seeding),which then propagates through neurons and glia(spreading).Existing data have been examined to establish why some neuronal populations are vulnerable while others are resistant to pathology and to what extent glia prevent and/or facilitate proteinopathy spreading.Connectomic approaches reveal a number of hubs in the olfactory system(anterior olfactory nucleus,olfactory entorhinal cortex and cortical amygdala)that are key interconnectors with the main hubs(the entorhinal–hippocampal–cortical and amygdala–dorsal motor vagal nucleus)of network dysfunction in Alzheimer’s and Parkinson’s diseases.
