In vivo neuroreceptor imaging and applications for Alzheimer's disease

S. J. Teipel, P. Bartenstein, G. E. Alexander, H. J. Moller, S. I. Rapoport, H. Hampel

Research output: Contribution to journalArticle

Abstract

A large body of evidence from neuropathological studies in Alzheimer's disease (AD) on postmortem brains has demonstrated impairment of specific neurotransmitter systems, especially of the cholinergic system. These studies, however, reflect end stages of the disease and permit only limited inference of the temporal sequence and cognitive and behavioral effects of deficits in neurotransmission. Since 1979, positron emission tomography (PET) has evolved into a powerful tool to visualize neuroreceptor binding in the living human brain and to quantify neuroreceptor density and ligand-receptor binding kinetics. Assessment of binding characteristics and receptor availability is essentially based on compartment models or saturation kinetic analysis derived from autoradiographic studies. This article describes the mathematical assumptions underlying these models and the biochemical characteristics that have to be met by a ligand to allow mapping of specific binding in PET. From this methodological basis, we review the present state of in vivo neuroreceptor imaging in AD. The majority of studies have focused on the cholinergic system, showing a decrease of nicotinic binding sites in frontal and temporal cortex in AD that was partially reversible through administration of central cholinergic drugs. As will be shown, interpretation of these results is severely limited by methodological difficulties. Recent studies have further demonstrated alterations of serotonin and opioid receptor availability in AD. We conclude with a discussion of the requirements that should be met by future studies on neurotransmission alterations in AD and outline possible future perspectives for these studies with respect to differential diagnosis and selective assessment of drug action and efficacy.

Original languageEnglish (US)
Pages (from-to)341-350
Number of pages10
JournalDrug News and Perspectives
Volume12
Issue number6
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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    Teipel, S. J., Bartenstein, P., Alexander, G. E., Moller, H. J., Rapoport, S. I., & Hampel, H. (1999). In vivo neuroreceptor imaging and applications for Alzheimer's disease. Drug News and Perspectives, 12(6), 341-350.