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Correlations between Alzheimer's Disease Cerebrospinal Fluid Biomarkers and Cerebral Glucose Metabolism after 12 Months of Phenserine Treatment
Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, S-14187 Huddinge, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, S-14187 Huddinge, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Translat Alzheimer Neurobiol, S-14187 Huddinge, Sweden.;Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden..
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2015 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 47, no 3, 691-704 p.Article in journal (Refereed) Published
Abstract [en]

New therapeutic strategies in Alzheimer's disease (AD) are focused on targeting amyloid-beta (A beta) to modify the underlying cause of the disease rather than just the symptoms. The aim of this study was to investigate the long-term effects of treatment with the anti-A beta compound phenserine on (i) cerebrospinal fluid (CSF) biomarkers for A beta and tau pathology and (ii) brain metabolism as assessed by the regional cerebral metabolic rate for glucose (rCMRglc), using positron emission tomography. Twenty patients with mild AD were included in the study and after 12 months treatment with phenserine, CSF A beta(40) and alpha- and beta-secretase-cleaved soluble amyloid-beta protein precursor (sA beta PP) levels had significantly increased and rCMRglc had stabilized. Levels of CSF A beta(40) and sA beta PP correlated positively with rCMRglc and cognition while CSF A beta(42) levels, the A beta(42/40) ratio, P-tau, and T-tau correlated negatively with rCMRglc and cognition. In summary, long-term phenserine treatment resulted in increased levels of CSF A beta(40), sA beta PP alpha, and sA beta PP beta, which positively correlated with improvements in rCMRglc and cognition. The study illustrates the value of using biomarkers in the CSF and brain for evaluation of drug effects.

Place, publisher, year, edition, pages
2015. Vol. 47, no 3, 691-704 p.
Keyword [en]
Alzheimer's disease, cerebral glucose metabolism, cerebrospinal fluid, phenserine, positron emission tomography
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-264341DOI: 10.3233/JAD-132474ISI: 000360930700015PubMedID: 26401704OAI: oai:DiVA.org:uu-264341DiVA: diva2:859978
Funder
Swedish Research Council, 05817Stockholm County Council
Available from: 2015-10-09 Created: 2015-10-09 Last updated: 2017-12-01Bibliographically approved

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Wall, Anders

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