ParkinsonCanadaV1, Main, Exploration, bibRecord, 001546

Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers

Identifieur interne : 001546 ( Main/Exploration ); précédent : 001545; suivant : 001547

Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers

Auteurs : J. O. Aasly [Norvège] ; M. Shi [États-Unis] ; V. Sossi [Canada] ; T. Stewart [États-Unis] ; K. K. Johansen [Norvège] ; Z. K. Wszolek [États-Unis] ; R. J. Uitti [États-Unis] ; K. Hasegawa [Japon] ; T. Yokoyama [Japon] ; C. P. Zabetian [États-Unis] ; H. M. Kim [États-Unis] ; J. B. Leverenz [États-Unis] ; C. Ginghina [États-Unis] ; J. Armaly [États-Unis] ; K. L. Edwards [États-Unis] ; K. W. Snapinn [États-Unis] ; A. J. Stoessl [Canada] ; J. Zhang [États-Unis]

Source :

Neurology [ 0028-3878 ] ; 2012.

RBID : Pascal:12-0105207

Descripteurs français

Pascal (Inist)
- Pathologie du système nerveux, Liquide céphalorachidien, Amyloïde, Mutation, Porteur.

English descriptors

KwdEn :
- Adult, Aged, Aged, 80 and over, Amyloid, Amyloid beta-Peptides (cerebrospinal fluid), Amyloid beta-Peptides (genetics), Biomarkers (cerebrospinal fluid), Carrier, Cerebrospinal fluid, Female, Genotype, Heterozygote, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Middle Aged, Mutation, Nervous system diseases, Parkinson Disease (cerebrospinal fluid), Parkinson Disease (diagnosis), Parkinson Disease (genetics), Peptide Fragments (cerebrospinal fluid), Peptide Fragments (genetics), Phenotype, Protein-Serine-Threonine Kinases (genetics), tau Proteins (cerebrospinal fluid), tau Proteins (genetics).
MESH :
- chemical , cerebrospinal fluid : Amyloid beta-Peptides, Biomarkers, Peptide Fragments, tau Proteins.
- chemical , genetics : Amyloid beta-Peptides, Peptide Fragments, Protein-Serine-Threonine Kinases, tau Proteins.
- cerebrospinal fluid : Parkinson Disease.
- diagnosis : Parkinson Disease.
- genetics : Parkinson Disease.
- Adult, Aged, Aged, 80 and over, Female, Genotype, Heterozygote, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Middle Aged, Mutation, Phenotype.

Abstract

Objective: The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid β (Aβ) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of Aβ and tau as markers of early or presymptomatic PD. Methods: CSF Aβ42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with ¹⁸F-6-fluoro-L-dopa (FD), ¹¹C-(±)-α-dihydrotetrabenazine (DTBZ), and ¹¹C-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement. Results: Reduced CSF Aβ42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between Aβ42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau. Conclusions: The disposition of Aβ and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers. I.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466497

Affiliations:

Le document en format XML

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<author><name sortKey="Johansen, K K" sort="Johansen, K K" uniqKey="Johansen K" first="K. K." last="Johansen">K. K. Johansen</name>
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<sZ>1 aut.</sZ>
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</inist:fA14>
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<sZ>6 aut.</sZ>
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<author><name sortKey="Uitti, R J" sort="Uitti, R J" uniqKey="Uitti R" first="R. J." last="Uitti">R. J. Uitti</name>
<affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurology (Z.K.W., R.J.U.), Mayo Clinic Florida</s1>
<s2>Jacksonville</s2>
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<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
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<author><name sortKey="Hasegawa, K" sort="Hasegawa, K" uniqKey="Hasegawa K" first="K." last="Hasegawa">K. Hasegawa</name>
<affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Neurology (K.H., T.Y.), National Hospital Organization, Sagamihara National Hospital</s1>
<s2>Kanagawa</s2>
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<sZ>8 aut.</sZ>
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<author><name sortKey="Yokoyama, T" sort="Yokoyama, T" uniqKey="Yokoyama T" first="T." last="Yokoyama">T. Yokoyama</name>
<affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Neurology (K.H., T.Y.), National Hospital Organization, Sagamihara National Hospital</s1>
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<s3>JPN</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Japon</country>
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</affiliation>
</author>
<author><name sortKey="Zabetian, C P" sort="Zabetian, C P" uniqKey="Zabetian C" first="C. P." last="Zabetian">C. P. Zabetian</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Neurology, University of Washington School of Medicine</s1>
<s2>Seattle</s2>
<s3>USA</s3>
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<wicri:noRegion>Parkinson's Disease Research, Education, and Clinical Center</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kim, H M" sort="Kim, H M" uniqKey="Kim H" first="H. M." last="Kim">H. M. Kim</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Neurology, University of Washington School of Medicine</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
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</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Parkinson's Disease Research, Education, and Clinical Center</s1>
<s3>USA</s3>
<sZ>10 aut.</sZ>
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<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Parkinson's Disease Research, Education, and Clinical Center</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Leverenz, J B" sort="Leverenz, J B" uniqKey="Leverenz J" first="J. B." last="Leverenz">J. B. Leverenz</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Neurology, University of Washington School of Medicine</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
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<country>États-Unis</country>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Psychiatry and Behavioral Sciences, University of Washington School of Medicine</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle</wicri:noRegion>
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<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Parkinson's Disease Research, Education, and Clinical Center</s1>
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<sZ>12 aut.</sZ>
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<wicri:noRegion>Parkinson's Disease Research, Education, and Clinical Center</wicri:noRegion>
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<affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Mental Illness Research, Education, and Clinical Center (J.B.L.), Veterans Affairs Puget Sound Health Care System</s1>
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<author><name sortKey="Ginghina, C" sort="Ginghina, C" uniqKey="Ginghina C" first="C." last="Ginghina">C. Ginghina</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Departments of Pathology, University of Washington School of Medicine</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
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<wicri:noRegion>Seattle</wicri:noRegion>
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<author><name sortKey="Armaly, J" sort="Armaly, J" uniqKey="Armaly J" first="J." last="Armaly">J. Armaly</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Departments of Pathology, University of Washington School of Medicine</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>18 aut.</sZ>
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<country>États-Unis</country>
<wicri:noRegion>Seattle</wicri:noRegion>
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<author><name sortKey="Edwards, K L" sort="Edwards, K L" uniqKey="Edwards K" first="K. L." last="Edwards">K. L. Edwards</name>
<affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Department of Epidemiology (K.L.E., K.W.S.), University of Washington School of Public Health</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Seattle</wicri:noRegion>
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<author><name sortKey="Snapinn, K W" sort="Snapinn, K W" uniqKey="Snapinn K" first="K. W." last="Snapinn">K. W. Snapinn</name>
<affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Department of Epidemiology (K.L.E., K.W.S.), University of Washington School of Public Health</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
<sZ>16 aut.</sZ>
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<country>États-Unis</country>
<wicri:noRegion>Seattle</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Stoessl, A J" sort="Stoessl, A J" uniqKey="Stoessl A" first="A. J" last="Stoessl">A. J. Stoessl</name>
<affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Pacific Parkinson's Research Centre (A.J.S.), University of British Columbia & Vancouver Coastal Health</s1>
<s2>Vancouver</s2>
<s3>CAN</s3>
<sZ>17 aut.</sZ>
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<country>Canada</country>
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<author><name sortKey="Zhang, J" sort="Zhang, J" uniqKey="Zhang J" first="J." last="Zhang">J. Zhang</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Departments of Pathology, University of Washington School of Medicine</s1>
<s2>Seattle</s2>
<s3>USA</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>18 aut.</sZ>
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<country>États-Unis</country>
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<series><title level="j" type="main">Neurology</title>
<title level="j" type="abbreviated">Neurology</title>
<idno type="ISSN">0028-3878</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Neurology</title>
<title level="j" type="abbreviated">Neurology</title>
<idno type="ISSN">0028-3878</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Amyloid</term>
<term>Amyloid beta-Peptides (cerebrospinal fluid)</term>
<term>Amyloid beta-Peptides (genetics)</term>
<term>Biomarkers (cerebrospinal fluid)</term>
<term>Carrier</term>
<term>Cerebrospinal fluid</term>
<term>Female</term>
<term>Genotype</term>
<term>Heterozygote</term>
<term>Humans</term>
<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Nervous system diseases</term>
<term>Parkinson Disease (cerebrospinal fluid)</term>
<term>Parkinson Disease (diagnosis)</term>
<term>Parkinson Disease (genetics)</term>
<term>Peptide Fragments (cerebrospinal fluid)</term>
<term>Peptide Fragments (genetics)</term>
<term>Phenotype</term>
<term>Protein-Serine-Threonine Kinases (genetics)</term>
<term>tau Proteins (cerebrospinal fluid)</term>
<term>tau Proteins (genetics)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" xml:lang="en"><term>Amyloid beta-Peptides</term>
<term>Biomarkers</term>
<term>Peptide Fragments</term>
<term>tau Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Amyloid beta-Peptides</term>
<term>Peptide Fragments</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>tau Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="cerebrospinal fluid" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Female</term>
<term>Genotype</term>
<term>Heterozygote</term>
<term>Humans</term>
<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Phenotype</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Pathologie du   système nerveux</term>
<term>Liquide céphalorachidien</term>
<term>Amyloïde</term>
<term>Mutation</term>
<term>Porteur</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Objective: The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid β (Aβ) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of Aβ and tau as markers of early or presymptomatic PD. Methods: CSF Aβ42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with <sup>18</sup>
F-6-fluoro-L-dopa (FD), <sup>11</sup>
C-(±)-α-dihydrotetrabenazine (DTBZ), and <sup>11</sup>
C-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement. Results: Reduced CSF Aβ42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between Aβ42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau. Conclusions: The disposition of Aβ and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers. I.</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>Japon</li>
<li>Norvège</li>
<li>États-Unis</li>
</country>
<region><li>Trøndelag</li>
</region>
<settlement><li>Trondheim</li>
</settlement>
</list>
<tree><country name="Norvège"><region name="Trøndelag"><name sortKey="Aasly, J O" sort="Aasly, J O" uniqKey="Aasly J" first="J. O." last="Aasly">J. O. Aasly</name>
</region>
<name sortKey="Aasly, J O" sort="Aasly, J O" uniqKey="Aasly J" first="J. O." last="Aasly">J. O. Aasly</name>
<name sortKey="Johansen, K K" sort="Johansen, K K" uniqKey="Johansen K" first="K. K." last="Johansen">K. K. Johansen</name>
<name sortKey="Johansen, K K" sort="Johansen, K K" uniqKey="Johansen K" first="K. K." last="Johansen">K. K. Johansen</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Shi, M" sort="Shi, M" uniqKey="Shi M" first="M." last="Shi">M. Shi</name>
</noRegion>
<name sortKey="Armaly, J" sort="Armaly, J" uniqKey="Armaly J" first="J." last="Armaly">J. Armaly</name>
<name sortKey="Edwards, K L" sort="Edwards, K L" uniqKey="Edwards K" first="K. L." last="Edwards">K. L. Edwards</name>
<name sortKey="Ginghina, C" sort="Ginghina, C" uniqKey="Ginghina C" first="C." last="Ginghina">C. Ginghina</name>
<name sortKey="Kim, H M" sort="Kim, H M" uniqKey="Kim H" first="H. M." last="Kim">H. M. Kim</name>
<name sortKey="Kim, H M" sort="Kim, H M" uniqKey="Kim H" first="H. M." last="Kim">H. M. Kim</name>
<name sortKey="Leverenz, J B" sort="Leverenz, J B" uniqKey="Leverenz J" first="J. B." last="Leverenz">J. B. Leverenz</name>
<name sortKey="Leverenz, J B" sort="Leverenz, J B" uniqKey="Leverenz J" first="J. B." last="Leverenz">J. B. Leverenz</name>
<name sortKey="Leverenz, J B" sort="Leverenz, J B" uniqKey="Leverenz J" first="J. B." last="Leverenz">J. B. Leverenz</name>
<name sortKey="Leverenz, J B" sort="Leverenz, J B" uniqKey="Leverenz J" first="J. B." last="Leverenz">J. B. Leverenz</name>
<name sortKey="Snapinn, K W" sort="Snapinn, K W" uniqKey="Snapinn K" first="K. W." last="Snapinn">K. W. Snapinn</name>
<name sortKey="Stewart, T" sort="Stewart, T" uniqKey="Stewart T" first="T." last="Stewart">T. Stewart</name>
<name sortKey="Uitti, R J" sort="Uitti, R J" uniqKey="Uitti R" first="R. J." last="Uitti">R. J. Uitti</name>
<name sortKey="Wszolek, Z K" sort="Wszolek, Z K" uniqKey="Wszolek Z" first="Z. K." last="Wszolek">Z. K. Wszolek</name>
<name sortKey="Zabetian, C P" sort="Zabetian, C P" uniqKey="Zabetian C" first="C. P." last="Zabetian">C. P. Zabetian</name>
<name sortKey="Zabetian, C P" sort="Zabetian, C P" uniqKey="Zabetian C" first="C. P." last="Zabetian">C. P. Zabetian</name>
<name sortKey="Zabetian, C P" sort="Zabetian, C P" uniqKey="Zabetian C" first="C. P." last="Zabetian">C. P. Zabetian</name>
<name sortKey="Zhang, J" sort="Zhang, J" uniqKey="Zhang J" first="J." last="Zhang">J. Zhang</name>
</country>
<country name="Canada"><noRegion><name sortKey="Sossi, V" sort="Sossi, V" uniqKey="Sossi V" first="V." last="Sossi">V. Sossi</name>
</noRegion>
<name sortKey="Stoessl, A J" sort="Stoessl, A J" uniqKey="Stoessl A" first="A. J" last="Stoessl">A. J. Stoessl</name>
</country>
<country name="Japon"><noRegion><name sortKey="Hasegawa, K" sort="Hasegawa, K" uniqKey="Hasegawa K" first="K." last="Hasegawa">K. Hasegawa</name>
</noRegion>
<name sortKey="Yokoyama, T" sort="Yokoyama, T" uniqKey="Yokoyama T" first="T." last="Yokoyama">T. Yokoyama</name>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson au Canada (serveur d'exploration)

Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers

Cerebrospinal fluid amyloid β and tau in LRRK2 mutation carriers

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	La maladie de Parkinson au Canada (serveur d'exploration)
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