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Titolo:
In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease
Autore:
Kuhl, DE; Koeppe, RA; Minoshima, S; Snyder, SE; Ficaro, EP; Foster, NL; Frey, KA; Kilbourn, MR;
Indirizzi:
Univ Michigan, Div Nucl Med, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 iv Nucl Med, Ann Arbor, MI 48109 USA Univ Michigan, Dept Neurol, Ann Arbor, MI USA Univ Michigan Ann Arbor MI USA Michigan, Dept Neurol, Ann Arbor, MI USA
Titolo Testata:
NEUROLOGY
fascicolo: 4, volume: 52, anno: 1999,
pagine: 691 - 699
SICI:
0028-3878(19990310)52:4<691:IVMOCA>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; IN-VIVO; CHOLINERGIC NEURONS; NERVOUS-SYSTEM; BLOOD-FLOW; BRAIN; PHARMACOKINETICS; PHYSOSTIGMINE; METABOLISM; VALIDATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Kuhl, DE UnivAMichigan Hosp, Div Nucl Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 US Univ Michigan Hosp 1500 E Med Ctr Dr Ann Arbor MI USA 48109 09 US
Citazione:
D.E. Kuhl et al., "In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease", NEUROLOGY, 52(4), 1999, pp. 691-699

Abstract

Objective: To validate an in vivo method for mapping acetylcholinesterase (AChE) activity in human brain, preparatory to monitoring inhibitor therapyin AD. Background: AChE activity is decreased in postmortem AD brain. Lacking a reliable in vivo measure, little is known about central activity in early AD, when the disease is commonly targeted by AChE inhibitor drug therapy. Methods: Intravenous N- [C-11]methylpiperidin-4-yl propionate ([C-11]PMP) served as an in vivo AChE substrate. AChE activity was defined using cerebral PET for tracer kinetic estimates of the local rate of [C-11]PMP hydrolysis in 26 normal controls and 14 patients with AD. Eleven AD patients also had concomitant in vivo cerebral measures of vesicular acetylcholine transporter (cholinergic terminal) density and glucose metabolism. Results: Cerebral AChE activity measures 1) were independent of changes in tracer delivery to cerebral cortex; 2) agreed with reported postmortem data concerning normal relative cerebral distributions, absence of large age-effect in normal aging, and deficits in AD; 3) correlated in AD cerebral cortex with concomitant in vivo measures of cholinergic terminal deficits, but not with metabolic deficits; and 4) agreed quantitatively with predicted level of cerebral AChE inhibition induced by physostimine. Conclusions: This in vivo PET method provided valid measures of central AChE activity in normal subjects and AD patients. Applied in early AD, it should facilitate inhibitor treatment by confirming central inhibition, optimizing drug dosage, identifying likely responders, and testing surrogate markers of therapeutic response.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 23:03:46