title: Correlations between Alzheimer's Disease Cerebrospinal Fluid Biomarkers and Cerebral Glucose Metabolism after 12 Months of Phenserine Treatment.
abstract: New therapeutic strategies in Alzheimer's disease (AD) are focused on targeting amyloid-β (Aβ) 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-Aβ compound phenserine on (i) cerebrospinal fluid (CSF) biomarkers for Aβ 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 Aβ40 and α- and β-secretase-cleaved soluble amyloid-β protein precursor (sAβPP) levels had significantly increased and rCMRglc had stabilized. Levels of CSF Aβ40 and sAβPP correlated positively with rCMRglc and cognition while CSF Aβ42 levels, the Aβ42/40 ratio, P-tau, and T-tau correlated negatively with rCMRglc and cognition. In summary, long-term phenserine treatment resulted in increased levels of CSF Aβ40, sAβPPα, and sAβPPβ, 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.
authors.affiliation: Karolinska Institutet, Dept NVS, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.affiliation: Karolinska Institutet, Dept NVS, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Huddinge, Sweden.|Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Ahmadul
authors.initials: A
authors.lastname: Kadir
authors.affiliation: Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.affiliation: Karolinska Institutet, Dept NVS, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Huddinge, Sweden.|Department of Psychology, Stockholm University, Stockholm, Sweden.
authors.forename: Ove
authors.initials: O
authors.lastname: Almkvist
authors.affiliation: Section of Nuclear Medicine & PET, Department of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wall
authors.affiliation: Department of Biochemistry and Organic Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.affiliation: Institute of Neuroscience and Physiology, Clinical Neurochemistry Laboratory, Göteborg University, Göteborg, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D013997:Time Factors; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C054369:MAPT protein, human; D018697:Nootropic Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D010830:Physostigmine; D005947:Glucose; C092280:phenserine
keywords: Alzheimer’s disease; cerebral glucose metabolism; cerebrospinal fluid; phenserine; positron emission tomography