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: Agneta Nordberg, Ahmadul Kadir, Niels Andreasen, Ove Almkvist, Anders Wall, Bengt Långström, Henrik Zetterberg
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 47 Issue 3 Pg. 691-704 ( 2015) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 26401704 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• APP protein, human
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Biomarkers
• MAPT protein, human
• Nootropic Agents
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• tau Proteins
• Physostigmine
• Glucose
• phenserine

Topics

• Aged
• Alzheimer Disease (diagnostic imaging, drug therapy, metabolism)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Amyloid beta-Protein Precursor (cerebrospinal fluid)
• Biomarkers (cerebrospinal fluid)
• Brain (diagnostic imaging, drug effects, metabolism)
• Cognition (drug effects, physiology)
• Double-Blind Method
• Female
• Glucose (metabolism)
• Humans
• Male
• Nootropic Agents (therapeutic use)
• Peptide Fragments (cerebrospinal fluid)
• Phosphorylation
• Physostigmine (analogs & derivatives, therapeutic use)
• Positron-Emission Tomography
• Time Factors
• Treatment Outcome
• tau Proteins (cerebrospinal fluid)