S-Adenosylmethionine is an essential ubiquitous metabolite central to many biochemical pathways, including transmethylation and polyamine biosynthesis. Reduced CSF S-adenosylmethionine levels in Alzheimer'sdisease have been reported; however, no information is available regarding the status of Sadenosylmethionine or S-adenosylmethionine-dependent methylation in the brain of patients with this disorder. S-Adenosylmethionine concentrations were measured in postmortem brain of 11 patients with Alzheimer's disease. We found decreased levels of S-adenosylmethionine(-67to -85%) and its demethylated product S-adenosylhomocysteine (-56 to -79%) in all brain areas examined (cerebral cortical subdivisions, hippocampus, and putamen) as compared with matched controls (n = 14). S-Adenosylmethionine and S-adenosylhomocysteine levels were normal in occipital cortex of patients with idiopathic Parkinson's disease (n = 10), suggesting that the decreased Sadenosylmethionine levels in Alzheimer's disease are not simply a consequence of a chronic, neurodegenerative condition. Reduced S-adenosylmethionine levels could be due to excessive utilization in polyamine biosynthesis. The severe reduction in levels of this essential biochemical substrate would be expected to compromise seriously metabolism and brain function in pa-

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Although experimental animal data have implicated ornithine decarboxylase, a key regulatory enzyme of polyamine biosynthesis, in brain development and function, little information is available on this enzyme in normal or abnormal human brain. We examined the influence, in autopsied human brain, of postnatal development and aging, regional distribution, and Alzheimer's disease on the activity of ornithine decarboxylase. Consistent with animal data, human brain ornithine decarboxylase activity was highest in the perinatal period, declining sharply (by '-60%) during the first year of life to values that remained generally unchanged up to senescence. In adult brain, a moderately heterogeneous regional distribution of enzyme activity was observed, with high levels in the thalamus and occipital cortex and low levels in cerebellar cortex and putamen. In the Alzheimer's disease group, mean ornithine decarboxylase activity was significantly increased in the temporal cortex (+76%), reduced in occipital cortex(-70%), and unchanged in hippocampus and putamen. In contrast, brain enzyme activity was normal in patients with the neurodegenerative disorder spinocerebellar ataxia type I. Our demonstration of ornithine decarboxylase activity in neonatal and adult human brain suggests roles for ornithine decarboxylase in both developing and mature brain function, and we provide further evidence for the involvement of abnormal polyamine system activity in Alzheimer's disease. Key Words: Human brain-Ornithine decarboxylase-Polyamine system-Development-Aging -Alzheimer's disease.

Although much evidence has implicated polyamines in brain development and function, little information is available on these substances in human brain. We examined the influence of regional distribution and aging on putrescine, spermidine, and spermine levels in autopsied human brain. In the adult brain, concentrations of spermidine were the highest, followed by spermine and putrescine. All three polyamines showed a distinct and uneven distribution profile among the 10 examined brain areas. Spermidine levels were especially high in white matter and thalamus (20 and 9.3 nmol/mg of protein, respectively), whereas spermine concentrations were highest in cerebellar cortex (3.4 nmol/mg of protein). High levels of putrescine were observed in cerebral cortices, putamen, and hippocampus (0.7–1.2 nmol/mg of protein), with lowest levels in cerebellum and thalamus (0.3–0.5 nmol/mg of protein). No statistically significant influence of aging (1 day to 103 years; n = 57) on either putrescine or spermine levels in occipital cortex was observed. In contrast, spermidine levels increased markedly from birth, reaching maximal levels at ∼40 years of age (+228% increase in the mean 41‐year‐old group vs. 6‐week‐old group), which were maintained up to senescence. These observations in human brain thus differ from those reported in the rodent, in which levels of all three polyamines show a pronounced postnatal reduction. Our data support the notion that polyamines may have roles in both postnatal brain development and in mature brain function.

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