Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia
Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease...
Saved in:
Published in | Brain (London, England : 1878) Vol. 138; no. Pt 9; pp. 2716 - 2731 |
---|---|
Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
01.09.2015
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-β1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-β1-42 and amyloid-β1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-β1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-β1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-β1-42 levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-β1-42, total tau, phosphorylated tau and the amyloid-β1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-β1-42 in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity. |
---|---|
AbstractList | Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-β1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-β1-42 and amyloid-β1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-β1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-β1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-β1-42 levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-β1-42, total tau, phosphorylated tau and the amyloid-β1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-β1-42 in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity. |
Author | Farahmand, Bahman Y Rosén, Christoffer Kilander, Lena Winblad, Bengt Zetterberg, Henrik Skillbäck, Tobias Mattsson, Niklas Schott, Jonathan M Wimo, Anders Nägga, Katarina Blennow, Kaj Eriksdotter, Maria Religa, Dorota |
Author_xml | – sequence: 1 givenname: Tobias surname: Skillbäck fullname: Skillbäck, Tobias email: tobias.skillback@neuro.gu.se organization: 1 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden tobias.skillback@neuro.gu.se – sequence: 2 givenname: Bahman Y surname: Farahmand fullname: Farahmand, Bahman Y organization: 2 Department of Neurobiology, Care Sciences, and Society (NVS), Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden – sequence: 3 givenname: Christoffer surname: Rosén fullname: Rosén, Christoffer organization: 1 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden – sequence: 4 givenname: Niklas surname: Mattsson fullname: Mattsson, Niklas organization: 1 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden 3 Department of Veterans Affairs Medical Centre, Centre for Imaging of Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, USA – sequence: 5 givenname: Katarina surname: Nägga fullname: Nägga, Katarina organization: 4 Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden – sequence: 6 givenname: Lena surname: Kilander fullname: Kilander, Lena organization: 5 Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden – sequence: 7 givenname: Dorota surname: Religa fullname: Religa, Dorota organization: 6 Department of Neurobiology, Care Sciences, and Society (NVS), Centre for Alzheimer Research, Division for Neurogeriatrtics, Karolinska Institutet, Huddinge, Sweden 7 Department Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden – sequence: 8 givenname: Anders surname: Wimo fullname: Wimo, Anders organization: 6 Department of Neurobiology, Care Sciences, and Society (NVS), Centre for Alzheimer Research, Division for Neurogeriatrtics, Karolinska Institutet, Huddinge, Sweden – sequence: 9 givenname: Bengt surname: Winblad fullname: Winblad, Bengt organization: 6 Department of Neurobiology, Care Sciences, and Society (NVS), Centre for Alzheimer Research, Division for Neurogeriatrtics, Karolinska Institutet, Huddinge, Sweden 7 Department Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden – sequence: 10 givenname: Jonathan M surname: Schott fullname: Schott, Jonathan M organization: 1 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden – sequence: 11 givenname: Kaj surname: Blennow fullname: Blennow, Kaj organization: 1 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden – sequence: 12 givenname: Maria surname: Eriksdotter fullname: Eriksdotter, Maria organization: 2 Department of Neurobiology, Care Sciences, and Society (NVS), Centre for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden 7 Department Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden – sequence: 13 givenname: Henrik surname: Zetterberg fullname: Zetterberg, Henrik organization: 1 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden 8 UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26133663$$D View this record in MEDLINE/PubMed https://gup.ub.gu.se/publication/222692$$DView record from Swedish Publication Index https://lup.lub.lu.se/record/7751105$$DView record from Swedish Publication Index http://kipublications.ki.se/Default.aspx?queryparsed=id:131996407$$DView record from Swedish Publication Index |
BookMark | eNp1kbtOHTEQhi1ExL1LHW2ZZsG39R6X0QmBSEeiIbU1tmeJk71lvZsjXisPkmdigAOiofjt8eifbzz2Mdvvhx4Z-yj4ueBWXfgJUn8B279iJfbYkdCGl1JUZv9NfMiOc_7FudBKmgN2KI1Qyhh1xL6ucUI_DXlMPbRF0y4pFjMsBfSxgO6-HVIs__8TpZZF6osR5oT9nIttmn8WETs6JDhlHxpoM57t9hP249vl7fq63NxcfV9_2ZSj5mYupdegERSn1hX3HKqwamLUIGwAZYKUmmQC1kaHyta1XdVSeI2G11XTVOqE2Wdu3uK4eDdOqYPp3g2QKB6i2-V_p0e5jE4oYa3RvKbazbu17TKSPOmxxspooIHoTBWs04YWq7h1yD29nwgaAydc-S7ujnCUunuiSZrISvJ_fvbTPf8smGfXpRywbaHHYclO1DRjpVa1IuunnXXxHcZX9MunqQdfa5u1 |
ContentType | Journal Article |
Copyright | The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
Copyright_xml | – notice: The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
DBID | CGR CUY CVF ECM EIF NPM 7X8 ADTPV AOWAS F1U D95 |
DOI | 10.1093/brain/awv181 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic SwePub SwePub Articles SWEPUB Göteborgs universitet SWEPUB Lunds universitet |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
DatabaseTitleList | MEDLINE - Academic MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1460-2156 |
EndPage | 2731 |
ExternalDocumentID | oai_prod_swepub_kib_ki_se_131996407 oai_lup_lub_lu_se_92d6afad_65c9_46c9_9309_e0b1431c4ec0 oai_gup_ub_gu_se_222692 26133663 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GeographicLocations | Sweden |
GeographicLocations_xml | – name: Sweden |
GroupedDBID | --- -E4 -~X .2P .55 .GJ .I3 .XZ .ZR 0R~ 1CY 1TH 23N 2WC 354 3O- 4.4 41~ 482 48X 53G 5GY 5RE 5VS 5WA 5WD 6.Y 6PF 70D AABZA AACZT AAGKA AAIMJ AAJKP AAJQQ AAMDB AAMVS AAOGV AAPGJ AAPNW AAPQZ AAPXW AAQQT AARHZ AAUAY AAUQX AAVAP AAVLN AAWDT AAWTL AAYJJ ABEUO ABIVO ABIXL ABJNI ABKDP ABLJU ABMNT ABNHQ ABNKS ABPTD ABQLI ABQNK ABQTQ ABSAR ABSMQ ABWST ABXVV ABZBJ ACBNA ACFRR ACGFS ACIWK ACPQN ACPRK ACUFI ACUTJ ACUTO ACYHN ACZBC ADBBV ADEYI ADEZT ADGKP ADGZP ADHKW ADHZD ADIPN ADJQC ADOCK ADQBN ADRIX ADRTK ADVEK ADYVW ADZXQ AEGPL AEHUL AEJOX AEKPW AEKSI AELWJ AEMDU AENEX AENZO AEPUE AETBJ AEWNT AFFNX AFFZL AFGWE AFIYH AFOFC AFSHK AFXAL AFXEN AFYAG AGINJ AGKEF AGKRT AGMDO AGQXC AGSYK AGUTN AHMBA AHXPO AI. AIJHB AJEEA AKWXX ALMA_UNASSIGNED_HOLDINGS ALUQC ANFBD APIBT APJGH APWMN AQDSO AQKUS ARIXL ASAOO ASPBG ATDFG ATGXG ATTQO AVNTJ AVWKF AXUDD AYOIW AZFZN BAWUL BAYMD BCRHZ BEYMZ BHONS BQDIO BR6 BSWAC BTRTY BVRKM BZKNY C1A C45 CAG CDBKE CGR COF CS3 CUY CVF CXTWN CZ4 DAKXR DFGAJ DIK DILTD DU5 D~K E3Z EBS ECM EE~ EIF EIHJH EJD ELUNK EMOBN ENERS F20 F5P F9B FECEO FEDTE FHSFR FLUFQ FOEOM FOTVD FQBLK G8K GAUVT GJXCC GX1 H13 H5~ HAR HVGLF HW0 HZ~ IOX J21 J5H JXSIZ KAQDR KBUDW KOP KQ8 KSI KSN L7B M-Z M49 MBLQV MBTAY MHKGH ML0 MVM N4W N9A NGC NLBLG NOMLY NOYVH NPM NTWIH NU- NVLIB O0~ O9- OAUYM OAWHX OBOKY OCZFY ODMLO OHH OHT OJQWA OJZSN OK1 OPAEJ OVD OWPYF O~Y P2P PAFKI PB- PEELM PQQKQ Q1. Q5Y QBD R44 RD5 RIG RNI ROL ROX ROZ RUSNO RW1 RXO RZF RZO TCN TCURE TEORI TJX TLC TMA TR2 VH1 VVN W8F WH7 WOQ X7H X7M XJT XOL YAYTL YKOAZ YQJ YSK YXANX ZCG ZGI ZKB ZKX ZXP ~91 7X8 AASNB ADTPV AOWAS F1U D95 |
ID | FETCH-LOGICAL-p406t-2b4a4ea3036650b0a5c8fdd4a19ca36c224c226ce764c597798721b4e6075ff53 |
ISSN | 1460-2156 |
IngestDate | Wed Oct 23 03:55:29 EDT 2024 Tue Oct 01 22:38:51 EDT 2024 Tue Oct 01 22:14:20 EDT 2024 Sun Sep 29 08:30:51 EDT 2024 Tue Oct 15 23:50:48 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | Pt 9 |
Keywords | dementia with Lewy bodies frontotemporal dementia Alzheimer’s disease biomarkers vascular dementia |
Language | English |
License | The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-p406t-2b4a4ea3036650b0a5c8fdd4a19ca36c224c226ce764c597798721b4e6075ff53 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
OpenAccessLink | https://academic.oup.com/brain/article-pdf/138/9/2716/13800222/awv181.pdf |
PMID | 26133663 |
PQID | 1707553873 |
PQPubID | 23479 |
PageCount | 16 |
ParticipantIDs | swepub_primary_oai_prod_swepub_kib_ki_se_131996407 swepub_primary_oai_lup_lub_lu_se_92d6afad_65c9_46c9_9309_e0b1431c4ec0 swepub_primary_oai_gup_ub_gu_se_222692 proquest_miscellaneous_1707553873 pubmed_primary_26133663 |
PublicationCentury | 2000 |
PublicationDate | 2015-09-01 |
PublicationDateYYYYMMDD | 2015-09-01 |
PublicationDate_xml | – month: 09 year: 2015 text: 2015-09-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | England |
PublicationPlace_xml | – name: England |
PublicationTitle | Brain (London, England : 1878) |
PublicationTitleAlternate | Brain |
PublicationYear | 2015 |
References | 26369513 - Nat Rev Neurol. 2015 Oct;11(10):549-50 |
References_xml | |
SSID | ssj0014326 |
Score | 2.5773995 |
Snippet | Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and... |
SourceID | swepub proquest pubmed |
SourceType | Open Access Repository Aggregation Database Index Database |
StartPage | 2716 |
SubjectTerms | Aged Amyloid beta-Peptides - cerebrospinal fluid Analysis of Variance Clinical Medicine Dementia - cerebrospinal fluid Enzyme-Linked Immunosorbent Assay Female Humans Klinisk medicin Male Medical and Health Sciences Medicin och hälsovetenskap Mental Status Schedule Middle Aged Neurologi Neurology Neurosciences Neurovetenskaper Peptide Fragments - cerebrospinal fluid Retrospective Studies Severity of Illness Index Sweden tau Proteins - cerebrospinal fluid |
Title | Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia |
URI | https://www.ncbi.nlm.nih.gov/pubmed/26133663 https://search.proquest.com/docview/1707553873 https://gup.ub.gu.se/publication/222692 https://lup.lub.lu.se/record/7751105 http://kipublications.ki.se/Default.aspx?queryparsed=id:131996407 |
Volume | 138 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLbQkBAviDvlpiAxXqqwxLGd-JF1rQZoCIlN2pvlW6ZoWTa1CUj8LH4Iv4njOGkbiATsIVblJHaU76tzzvG5IPRaUpNhWHtDnOYkJFjloeLGhFZRBeJECnc5RfHoEzs8IR9O6emmZmsbXVKrt_r7aFzJdVCFPsDVRcn-B7LrQaEDfgO-0ALC0P4TxjO7BJXWVf5wMmVeNoWZ1rLxCVgvQBUvTLg7m-_uY9Dg8HSTRrWLaTOtbbCQg51dVzNitNCHtx5kabZlPfhyXpSlknrob71wZuaLzmVyfy0suyqO1cAy66qNr_qYr20DREzXHlb9mklYFILkwAaLapJtsedzPeXbq2Tq4yv_WL59aiu1bI0iC_nta-zruYykxHbfF-GTu4rzwh1iZUWcOK9q4tIL3MQpp87J8-D9x_W-EklwF2_mH7kLhYB599pZ9_ycY-rGb7lkW_nj-C660ykOwTvPgnvohq3uo1tHnWvEA3QwIEPQkiEAMgQAQ9CT4ecPR4SgqIKeCIEjQtAT4SE6WcyPZ4dhVyIjvAJJrA6xIpJY6eQQELVVJKnOcmOIjLmWCdMgoMHBtE0Z0S7VIM9A5VfEMhAV85wmj9BOdVnZJyjALE2pNjFRmhNCbZbz3MbGShmDlkD1BL3q34mAJcjtK8nKXjYrEacwGHw402SCHvuXBfC0uVIEKOgJPBucedOB1Z9xIJ41VwK6zhqHHUiqjOMJmo9cWMKFJfSV7ZUcGyZzaQSjmgvCoOFJxIWNFCAca2J1NEF4ZJy_sObpdW56hm5v_hbP0U69bOwLkFRr9bIl3y_lrJhr |
link.rule.ids | 230,315,786,790,891,27955,27956 |
linkProvider | Flying Publisher |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cerebrospinal+fluid+tau+and+amyloid-%CE%B21-42+in+patients+with+dementia&rft.jtitle=Brain+%28London%2C+England+%3A+1878%29&rft.au=Skillback%2C+T&rft.au=Farahmand%2C+BY&rft.au=Rosen%2C+C&rft.au=Mattsson%2C+N&rft.date=2015-09-01&rft.issn=1460-2156&rft.volume=138&rft.issue=Pt+9&rft.spage=2716&rft_id=info:doi/10.1093%2Fbrain%2Fawv181&rft.externalDocID=oai_prod_swepub_kib_ki_se_131996407 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1460-2156&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1460-2156&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1460-2156&client=summon |