Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.
Identifieur interne : 000088 ( PubMed/Corpus ); précédent : 000087; suivant : 000089Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.
Auteurs : Lilian Calder N-Garcidue As ; José Avila-Ramírez ; Ana Calder N-Garcidue As ; Tonatiuh González-Heredia ; Hilda Acu A-Ayala ; Chih-Kai Chao ; Charles Thompson ; Rubén Ruiz-Ramos ; Victor Cortés-González ; Luz Martínez-Martínez ; Mario Alberto García-Pérez ; Jacques Reis ; Partha S. Mukherjee ; Ricardo Torres-Jard N ; Ingolf LachmannSource :
- Journal of Alzheimer's disease : JAD [ 1875-8908 ] ; 2016.
Abstract
Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-β (Aβ)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), Aβ1-42, α-synuclein (t-α-syn and d-α-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. Aβ1-42 and BDNF concentrations were significantly lower in MCMA children versus controls (p = 0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age (R2 = 0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-α-synuclein showed a significant correlation with TNFα, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R2 = 0.47), while d-α-synuclein exhibited a tendency to increase with cumulated PM2.5 (R2 = 0.30). CSF Aβ1-42, BDNF, α-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority.
DOI: 10.3233/JAD-160472
PubMed: 27567860
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.</title><author><name sortKey="Calder N Garcidue As, Lilian" sort="Calder N Garcidue As, Lilian" uniqKey="Calder N Garcidue As L" first="Lilian" last="Calder N-Garcidue As">Lilian Calder N-Garcidue As</name><affiliation><nlm:affiliation>The University of Montana, Missoula, MT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Avila Ramirez, Jose" sort="Avila Ramirez, Jose" uniqKey="Avila Ramirez J" first="José" last="Avila-Ramírez">José Avila-Ramírez</name><affiliation><nlm:affiliation>Médica Sur, Mexico City, México.</nlm:affiliation></affiliation></author><author><name sortKey="Calder N Garcidue As, Ana" sort="Calder N Garcidue As, Ana" uniqKey="Calder N Garcidue As A" first="Ana" last="Calder N-Garcidue As">Ana Calder N-Garcidue As</name><affiliation><nlm:affiliation>Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Gonzalez Heredia, Tonatiuh" sort="Gonzalez Heredia, Tonatiuh" uniqKey="Gonzalez Heredia T" first="Tonatiuh" last="González-Heredia">Tonatiuh González-Heredia</name><affiliation><nlm:affiliation>Universidad del Valle de México, México.</nlm:affiliation></affiliation></author><author><name sortKey="Acu A Ayala, Hilda" sort="Acu A Ayala, Hilda" uniqKey="Acu A Ayala H" first="Hilda" last="Acu A-Ayala">Hilda Acu A-Ayala</name><affiliation><nlm:affiliation>Universidad del Valle de México, México.</nlm:affiliation></affiliation></author><author><name sortKey="Chao, Chih Kai" sort="Chao, Chih Kai" uniqKey="Chao C" first="Chih-Kai" last="Chao">Chih-Kai Chao</name><affiliation><nlm:affiliation>The University of Montana, Missoula, MT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Thompson, Charles" sort="Thompson, Charles" uniqKey="Thompson C" first="Charles" last="Thompson">Charles Thompson</name><affiliation><nlm:affiliation>The University of Montana, Missoula, MT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ruiz Ramos, Ruben" sort="Ruiz Ramos, Ruben" uniqKey="Ruiz Ramos R" first="Rubén" last="Ruiz-Ramos">Rubén Ruiz-Ramos</name><affiliation><nlm:affiliation>Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Cortes Gonzalez, Victor" sort="Cortes Gonzalez, Victor" uniqKey="Cortes Gonzalez V" first="Victor" last="Cortés-González">Victor Cortés-González</name><affiliation><nlm:affiliation>Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Martinez Martinez, Luz" sort="Martinez Martinez, Luz" uniqKey="Martinez Martinez L" first="Luz" last="Martínez-Martínez">Luz Martínez-Martínez</name><affiliation><nlm:affiliation>Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Garcia Perez, Mario Alberto" sort="Garcia Perez, Mario Alberto" uniqKey="Garcia Perez M" first="Mario Alberto" last="García-Pérez">Mario Alberto García-Pérez</name><affiliation><nlm:affiliation>Hospital Regional de Alta Especialidad, Ciudad Victoria, Tamaulipas, México.</nlm:affiliation></affiliation></author><author><name sortKey="Reis, Jacques" sort="Reis, Jacques" uniqKey="Reis J" first="Jacques" last="Reis">Jacques Reis</name><affiliation><nlm:affiliation>Service de Neurologie, Centre Hospitalier Universitaire, Hôpital de Hautepierre, Strasbourg, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mukherjee, Partha S" sort="Mukherjee, Partha S" uniqKey="Mukherjee P" first="Partha S" last="Mukherjee">Partha S. Mukherjee</name><affiliation><nlm:affiliation>Mathematics Department, Boise State University, Boise, ID, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Torres Jard N, Ricardo" sort="Torres Jard N, Ricardo" uniqKey="Torres Jard N R" first="Ricardo" last="Torres-Jard N">Ricardo Torres-Jard N</name><affiliation><nlm:affiliation>Universidad Nacional Autónoma de México, Mexico City, México.</nlm:affiliation></affiliation></author><author><name sortKey="Lachmann, Ingolf" sort="Lachmann, Ingolf" uniqKey="Lachmann I" first="Ingolf" last="Lachmann">Ingolf Lachmann</name><affiliation><nlm:affiliation>AJ Roboscreen GmbH, Leipzig, Germany.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27567860</idno><idno type="pmid">27567860</idno><idno type="doi">10.3233/JAD-160472</idno><idno type="wicri:Area/PubMed/Corpus">000088</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000088</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.</title><author><name sortKey="Calder N Garcidue As, Lilian" sort="Calder N Garcidue As, Lilian" uniqKey="Calder N Garcidue As L" first="Lilian" last="Calder N-Garcidue As">Lilian Calder N-Garcidue As</name><affiliation><nlm:affiliation>The University of Montana, Missoula, MT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Avila Ramirez, Jose" sort="Avila Ramirez, Jose" uniqKey="Avila Ramirez J" first="José" last="Avila-Ramírez">José Avila-Ramírez</name><affiliation><nlm:affiliation>Médica Sur, Mexico City, México.</nlm:affiliation></affiliation></author><author><name sortKey="Calder N Garcidue As, Ana" sort="Calder N Garcidue As, Ana" uniqKey="Calder N Garcidue As A" first="Ana" last="Calder N-Garcidue As">Ana Calder N-Garcidue As</name><affiliation><nlm:affiliation>Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Gonzalez Heredia, Tonatiuh" sort="Gonzalez Heredia, Tonatiuh" uniqKey="Gonzalez Heredia T" first="Tonatiuh" last="González-Heredia">Tonatiuh González-Heredia</name><affiliation><nlm:affiliation>Universidad del Valle de México, México.</nlm:affiliation></affiliation></author><author><name sortKey="Acu A Ayala, Hilda" sort="Acu A Ayala, Hilda" uniqKey="Acu A Ayala H" first="Hilda" last="Acu A-Ayala">Hilda Acu A-Ayala</name><affiliation><nlm:affiliation>Universidad del Valle de México, México.</nlm:affiliation></affiliation></author><author><name sortKey="Chao, Chih Kai" sort="Chao, Chih Kai" uniqKey="Chao C" first="Chih-Kai" last="Chao">Chih-Kai Chao</name><affiliation><nlm:affiliation>The University of Montana, Missoula, MT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Thompson, Charles" sort="Thompson, Charles" uniqKey="Thompson C" first="Charles" last="Thompson">Charles Thompson</name><affiliation><nlm:affiliation>The University of Montana, Missoula, MT, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ruiz Ramos, Ruben" sort="Ruiz Ramos, Ruben" uniqKey="Ruiz Ramos R" first="Rubén" last="Ruiz-Ramos">Rubén Ruiz-Ramos</name><affiliation><nlm:affiliation>Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Cortes Gonzalez, Victor" sort="Cortes Gonzalez, Victor" uniqKey="Cortes Gonzalez V" first="Victor" last="Cortés-González">Victor Cortés-González</name><affiliation><nlm:affiliation>Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Martinez Martinez, Luz" sort="Martinez Martinez, Luz" uniqKey="Martinez Martinez L" first="Luz" last="Martínez-Martínez">Luz Martínez-Martínez</name><affiliation><nlm:affiliation>Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.</nlm:affiliation></affiliation></author><author><name sortKey="Garcia Perez, Mario Alberto" sort="Garcia Perez, Mario Alberto" uniqKey="Garcia Perez M" first="Mario Alberto" last="García-Pérez">Mario Alberto García-Pérez</name><affiliation><nlm:affiliation>Hospital Regional de Alta Especialidad, Ciudad Victoria, Tamaulipas, México.</nlm:affiliation></affiliation></author><author><name sortKey="Reis, Jacques" sort="Reis, Jacques" uniqKey="Reis J" first="Jacques" last="Reis">Jacques Reis</name><affiliation><nlm:affiliation>Service de Neurologie, Centre Hospitalier Universitaire, Hôpital de Hautepierre, Strasbourg, France.</nlm:affiliation></affiliation></author><author><name sortKey="Mukherjee, Partha S" sort="Mukherjee, Partha S" uniqKey="Mukherjee P" first="Partha S" last="Mukherjee">Partha S. Mukherjee</name><affiliation><nlm:affiliation>Mathematics Department, Boise State University, Boise, ID, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Torres Jard N, Ricardo" sort="Torres Jard N, Ricardo" uniqKey="Torres Jard N R" first="Ricardo" last="Torres-Jard N">Ricardo Torres-Jard N</name><affiliation><nlm:affiliation>Universidad Nacional Autónoma de México, Mexico City, México.</nlm:affiliation></affiliation></author><author><name sortKey="Lachmann, Ingolf" sort="Lachmann, Ingolf" uniqKey="Lachmann I" first="Ingolf" last="Lachmann">Ingolf Lachmann</name><affiliation><nlm:affiliation>AJ Roboscreen GmbH, Leipzig, Germany.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of Alzheimer's disease : JAD</title><idno type="eISSN">1875-8908</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-β (Aβ)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), Aβ1-42, α-synuclein (t-α-syn and d-α-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. Aβ1-42 and BDNF concentrations were significantly lower in MCMA children versus controls (p = 0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age (R2 = 0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-α-synuclein showed a significant correlation with TNFα, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R2 = 0.47), while d-α-synuclein exhibited a tendency to increase with cumulated PM2.5 (R2 = 0.30). CSF Aβ1-42, BDNF, α-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">27567860</PMID><DateCreated><Year>2016</Year><Month>09</Month><Day>10</Day></DateCreated><DateRevised><Year>2016</Year><Month>09</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1875-8908</ISSN><JournalIssue CitedMedium="Internet"><Volume>54</Volume><Issue>2</Issue><PubDate><Year>2016</Year><Month>Sep</Month><Day>06</Day></PubDate></JournalIssue><Title>Journal of Alzheimer's disease : JAD</Title><ISOAbbreviation>J. Alzheimers Dis.</ISOAbbreviation></Journal><ArticleTitle>Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents.</ArticleTitle><Pagination><MedlinePgn>597-613</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3233/JAD-160472</ELocationID><Abstract><AbstractText>Exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-β (Aβ)1 - 42 diffuse plaques, and aggregated and hyperphosphorylated α-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), Aβ1-42, α-synuclein (t-α-syn and d-α-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. Aβ1-42 and BDNF concentrations were significantly lower in MCMA children versus controls (p = 0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 μg/m3 and then decreased, regardless of cumulative value or age (R2 = 0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-α-synuclein showed a significant correlation with TNFα, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R2 = 0.47), while d-α-synuclein exhibited a tendency to increase with cumulated PM2.5 (R2 = 0.30). CSF Aβ1-42, BDNF, α-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Calderón-Garcidueñas</LastName><ForeName>Lilian</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>The University of Montana, Missoula, MT, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Universidad del Valle de México, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Avila-Ramírez</LastName><ForeName>José</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Médica Sur, Mexico City, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Calderón-Garcidueñas</LastName><ForeName>Ana</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>González-Heredia</LastName><ForeName>Tonatiuh</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Universidad del Valle de México, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Acuña-Ayala</LastName><ForeName>Hilda</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Universidad del Valle de México, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chao</LastName><ForeName>Chih-Kai</ForeName><Initials>CK</Initials><AffiliationInfo><Affiliation>The University of Montana, Missoula, MT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thompson</LastName><ForeName>Charles</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>The University of Montana, Missoula, MT, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ruiz-Ramos</LastName><ForeName>Rubén</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Instituto de Medicina Forense, Universidad Veracruzana, Boca del Río, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cortés-González</LastName><ForeName>Victor</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Martínez-Martínez</LastName><ForeName>Luz</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Hospital de Especialidades No. 14, I.M.S.S, Boca del Río, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>García-Pérez</LastName><ForeName>Mario Alberto</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Hospital Regional de Alta Especialidad, Ciudad Victoria, Tamaulipas, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reis</LastName><ForeName>Jacques</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Service de Neurologie, Centre Hospitalier Universitaire, Hôpital de Hautepierre, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mukherjee</LastName><ForeName>Partha S</ForeName><Initials>PS</Initials><AffiliationInfo><Affiliation>Mathematics Department, Boise State University, Boise, ID, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Torres-Jardón</LastName><ForeName>Ricardo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Universidad Nacional Autónoma de México, Mexico City, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lachmann</LastName><ForeName>Ingolf</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>AJ Roboscreen GmbH, Leipzig, Germany.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Alzheimers Dis</MedlineTA><NlmUniqueID>9814863</NlmUniqueID><ISSNLinking>1387-2877</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Air pollution</Keyword><Keyword MajorTopicYN="N">Alzheimer’s disease</Keyword><Keyword MajorTopicYN="N">BDNF</Keyword><Keyword MajorTopicYN="N">Mexico City</Keyword><Keyword MajorTopicYN="N">PM2.5</Keyword><Keyword MajorTopicYN="N">Parkinson</Keyword><Keyword MajorTopicYN="N">amyloid-β1–42</Keyword><Keyword MajorTopicYN="N">cerebrospinal fluid</Keyword><Keyword MajorTopicYN="N">children</Keyword><Keyword MajorTopicYN="N">insulin</Keyword><Keyword MajorTopicYN="N">leptin</Keyword><Keyword MajorTopicYN="N">prion cellular protein</Keyword><Keyword MajorTopicYN="N">α-synuclein</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>8</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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