Neurobiologyof Aging, Vol. 2, pp. 57--60, 1981. Printed in the U.S.A. Central Amine Metabolism in Alzheimer's Disease: In Vivo Relationship to Cognitive Deficit I J. JOHN MANN, =* MICHAEL STANLEY,* ANDREAS NEOPHYTIDES,:~ MONY J. DE LEON,t STEVEN H. FERRIS* AND SAMUEL GERSHON 3 *Payne Whitney Clinic, New York HospitaI-Cornell University Medical College 525 East 68th Street, New York, NY and erDepartment of Psychiatry and $Department of Neurology New York University Medical Center, 550 First Avenue, New York, NY Received 5 January 1981 MANN, J. J., M. STANLEY, A. NEOPHYTIDES, M. J. DE LEON, S. H. FERRIS AND S. GERSHON. Centralamine metabolism in AIzheimer's disease: In vivo relationship to cognitive deficit. NEUROBIOL. AGING 2(1) 57-60, 1981.--Levels of the amine metabolites homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) were meas- ured in the cerebrospinal ~CSF) fluid of drug-free patients with Aizheimer's disease and compared to levels in a group of controls. No significant differences were found in CSF HVA and MHPG, although the Alzheimer's group was severely demented. Platelet monoamine oxidase (MAO) enzyme kinetics were measured and did not differ between controls and Alzheimer patients. The degree of dementia did not show any significant correlation with the levels of HVA or MHPG. It was concluded that, unlike previous reports in the literature, the dementia of Alzheimer's disease was not related to changes in central catecholamine metabolism nor was it associated with increased platelet MAO activity: Alzheimer's disease Cerebrospinal fluid Homovanillic acid Platelet monoamine oxidase activity CT scan Methoxyhydroxyphenylglycol THE presence of diffuse cerebral atrophy in dementia due to Alzheimer's disease (AD) suggests that multiple neuro- transmitter systems may be involved. There are now well confirmed findings of reduced levels of choline acetyl- transferase activity in AD [6, 17, 26]. This deficit has been correlated with other changes in AD such as plaque count, degree of cerebral atrophy and cognitive deficit [23]. The pharmacological effects of altering central cholinergic activ- ity in altering cognitive function are consistent with a role for acetyicholine in memory processes [4,9]. Studies ofCNS aminergic systems in AD are preliminary, and less definite. It appears that there is evidence for an age-related decline in levels of NE, DA and 5-HT [2, 12, 20] in some brain regions and an increase in MAO B levels [12,21] with age. A report that these changes may be greater still in patients with AD [1] is largely unconfirmed, and one study in fact reported normal levels of DA in this disease [26]. The finding of significantly reduced levels of HVA in the CSF of younger patients with AD was consistent with the postmortem data but was not confirmed in an older group of patients with AD [13]. In addition there is a body of animal data supporting a role for NE and DA in cognitive functions [3, 18, 19, 22] as well as the results of treatment of cognitive deficits in humans using L-dopa and stimulants such as am- phetamines (that probably act via aminergic mechanisms) [5,10]. However apart from the reports of Gottfries and col- leagues there is a lack of other direct biochemical evidence to corroborate their findings of an aminergic lesion in AD. We decided to investigate the relationship of central amine metabolism to cognitive deficit in AD in vivo so that both biochemical and cognitive measures could be per- formed concurrently. A group of severely demented patients was selected in order to increase the probability of detecting any disease-related biochemical changes. As platelet and brain MAO type B activity have been reported to increase with age [21] and even further elevated in AD [1], we also measured platelet MAO enzyme kinetics and examined their relationship to central amine metabo- lism. Since DA is an MAO type-B substrate in human brain [11] and platelet MAO is about 98c~ type-B [8], it was possi- ble that platelet MAO may reflect changes in brain MAO type B activity and thereby levels of CSF HVA. Computerized tomography (CT) was used not only for ~Pan of this data was presented at the 12th CINP Congress Goltenberg, Sweden, July, 1980. ~Send repreint requests to J. John Mann. M.D. Payne Whitney Clinic, New York Hospital-Cornell University Medical College, 525 East 68th Street, New York, New York, 10021, USA. aNow at the Department of Psychiatry, Wayne State University, Detroit, Michigan. Copyright ~ 1981 ANKHO International Inc.--0197-4580/81/010057-04500.90/0