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Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
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2010 (English)In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 29, no 3, 204-212 p.Article in journal (Refereed) Published
Abstract [en]

Background:

The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring β-amyloid (Aβ) load. Associations between PET PIB and cerebrospinal fluid (CSF) Aβ1–42 and apolipoprotein E ε4 (APOE ε4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer’s disease (AD) are less investigated.

Method:

PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD.

Results:

PIB retention was constant over 1 year, inversely related to low CSF Aβ1–42 (p = 0.01) and correlated positively to the numbers of the APOE ε4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = –0.59, p = 0.07), and plasma cystatin C (r = –0.56, p = 0.09).

Conclusion:

PIB retention is strongly related to CSF Aβ1–42, and to the numbers of the APOE ε4 allele.

Place, publisher, year, edition, pages
2010. Vol. 29, no 3, 204-212 p.
National Category
Medical and Health Sciences Geriatrics
Identifiers
URN: urn:nbn:se:uu:diva-132548DOI: 10.1159/000281832ISI: 000276783100003PubMedID: 20332638OAI: oai:DiVA.org:uu-132548DiVA: diva2:358275
Available from: 2010-10-21 Created: 2010-10-21 Last updated: 2014-05-22Bibliographically approved
In thesis
1. Biomarkers as Monitors of Drug Effect, Diagnostic Tools and Predictors of Deterioration Rate in Alzheimer’s Disease
Open this publication in new window or tab >>Biomarkers as Monitors of Drug Effect, Diagnostic Tools and Predictors of Deterioration Rate in Alzheimer’s Disease
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Decreased amyloid-ß42 (Aß42), increased total tau (t-tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) reflect histopathological core changes in the most common dementia disorder, Alzheimer’s disease (AD). They discriminate AD from healthy controls and predict conversion to AD with a relatively high accuracy. Memantine, an uncompetitive NMDA-receptor antagonist, is indicated for symptomatic treatment of AD. The first aim of this thesis was to investigate effects of memantine on CSF concentrations of Aβ42, tau and p-tau. Secondly, the aim was to explore the relation between these CSF biomarkers and retention of the amyloid biomarker Pittsburgh compound B using positron emission tomography (PIB PET), regional glucose metabolism measured with 18Fluoro-2-deoxy-d-glucose (FDG) PET and neuropsychological test performance. The third aim was to investigate their possible utility as predictors of future rate of AD dementia deterioration. All patients in the studies were recruited from the Memory Clinic, Uppsala University Hospital. In study I CSF p-tau concentrations in 11 AD patients were reduced after twelve months treatment with memantine, indicating that this compound may affect a key pathological process in AD. Results from study II showed that the concentrations of CSF Aß42 are lower in PIB+ patients than in PIB- patients, and that the PIB retention was stable during 12 months. In study III 10 patients with the diagnoses AD (6 PIB+/4 PIB-) and 8 subjects (1 PIB+/7 PIB-) with frontotemporal dementia were included. PIB+ patients had lower psychomotor speed measured by performance on the Trail Making Test A and impaired visual episodic memory compared to the PIB- patients. The initial clinical diagnoses were changed in 33% of the patients (6/18) during follow-up. Study IV is the first-ever report of an association between high CSF tau and dying in severe dementia. These 196 AD patients were followed up to nine years after baseline lumbar puncture. Moreover, CSF t-tau concentrations above median was associated with an increased risk of rapid cognitive decline (OR 3.31 (95% CI 1.53-7.16), independently of baseline functional stage. Thus, a clear association between high levels of CSF t-tau and p-tau and a more aggressive course of the disease was shown.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 881
Keyword
Alzheimer's disease, biomarkers, CSF, PIB PET, amyloid-beta, tau, rapid cognitive decline, dying in severe dementia, mortality, neuropsychological tests
National Category
Geriatrics
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-196965 (URN)978-91-554-8629-7 (ISBN)
Public defence
2013-05-16, Enghoffsalen, Ingång 50, bv, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2013-04-24 Created: 2013-03-15 Last updated: 2013-08-30Bibliographically approved

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Degerman Gunnarsson, MalinWall, AndersBasu, SamarLarsson, AndersLannfelt, LarsKilander, Lena

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