{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:12:34Z","timestamp":1790071954190,"version":"4.0.1"},"reference-count":32,"publisher":"BMJ","issue":"6422","license":[{"start":{"date-parts":[[1984,3,31]],"date-time":"1984-03-31T00:00:00Z","timestamp":449539200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.bmj.com\/company\/legal-information\/terms-conditions\/legal-information\/tdm-licencepolicy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br Med J (Clin Res Ed)"],"published-print":{"date-parts":[[1984,3,31]]},"abstract":"<jats:p>Brains of 49 patients who had died with Alzheimer's disease and 54 controls were examined. The Alzheimer group exhibited noticeably reduced activity of the cholinergic marker enzyme choline acetyltransferase in the cerebral cortex, but cortical concentrations of noradrenaline, gamma-aminobutyric acid, and somatostatin were also significantly reduced. Analysis of the results according to age at death showed that the older patients, dying in their 9th and 10th decades, had a relatively pure cholinergic deficit confined to temporal lobe and hippocampus, together with a reduced concentration of somatostatin confined to temporal cortex. By contrast, the younger patients, dying in their 7th and 8th decades, had a widespread and severe cholinergic deficit together with the abnormalities of noradrenaline, gamma-aminobutyric acid, and somatostatin, and the younger patients accounted for most of the abnormalities in these systems observed in the overall group. Comparison of the young subjects with Alzheimer's disease with the older controls did not support the concept of Alzheimer's disease representing an acceleration of the aging process. These results suggest that Alzheimer's disease in people aged under 80 may represent a distinct form of presenile dementia which differs in important respects from the dementia of old age.<\/jats:p>","DOI":"10.1136\/bmj.288.6422.961","type":"journal-article","created":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T11:00:59Z","timestamp":1238670059000},"page":"961-964","source":"Crossref","is-referenced-by-count":352,"title":["Neurochemical characteristics of early and late onset types of Alzheimer's disease."],"prefix":"10.1136","volume":"288","author":[{"given":"M N","family":"Rossor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L L","family":"Iversen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G P","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Q","family":"Mountjoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1984,3,31]]},"reference":[{"issue":"36","key":"ref_1","first-page":"293","article-title":"Clinicopathologic study of Alzheimer's disease: relationship to senile condition","volume":"1936","author":"D, I.Rothschild; J, Kasansin","unstructured":"I Rothschild D, Kasansin J. Clinicopathologic study of Alzheimer's disease: relationship to senile condition. Archives of Neurology and Psychiatry 1936;36:293-321.","journal-title":"Archives of Neurology and Psychiatry"},{"key":"ref_2","article-title":"Mental illness and the ageing brain","author":"Corsellis, J.A.N.","year":"9.)","unstructured":"Corsellis JAN. Mental illness and the ageing brain. Oxford: University Press, 1962:45. (Maudsley Monograph No 9.)"},{"key":"ref_3","first-page":"135","volume":"50","author":"Sci, Neurol","year":"1981","unstructured":"Neurol Sci 1981;50:135-45."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0197-4580(83)90048-9","article-title":"Cortical neuronal counts in normal elderly controls and demented patients","volume":"4","author":"iMountjoy CQ; M, Roth; NJR, Evans; HM, Evans","year":"1983","unstructured":"iMountjoy CQ, Roth M, Evans NJR, Evans HM. Cortical neuronal counts in normal elderly controls and demented patients. Neuirobiol Aging 1983;4: 1 - 11.","journal-title":"Neuirobiol Aging"},{"key":"ref_5","article-title":"The concept of Alzheimer's disease and its clinical implications","volume-title":"disease and related conditions","author":"Sourander, P.; Sjogren, H.","year":"1970","unstructured":"Sourander P, Sjogren H. The concept of Alzheimer's disease and its clinical implications. In: Wolstenholme GW, O'Connor M, eds. Alzheimer's disease and related conditions. London: Churchill, 1970."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1001\/archneur.1983.04050030037006","article-title":"A comparison of clinical features in earlyand late-onset primary degenerative dementia","volume":"40","author":"Seltzer, B.; Sherwin, I.","year":"1983","unstructured":"Seltzer B, Sherwin I. A comparison of clinical features in earlyand late-onset primary degenerative dementia. Arch Neuirol 1983;40:143-6.","journal-title":"Arch Neuirol"},{"key":"ref_7","first-page":"135","article-title":"The cholinergic system in Alzheimer's discase","volume-title":"Biochempiistry of dementia","author":"Perry, E.K.; Perry, R.H.","year":"1980","unstructured":"Perry EK, Perry RH. The cholinergic system in Alzheimer's discase. In: Roberts PJ, ed. Biochempiistry of dementia. Chichester: John Wiley and Sons, 1980:135-83."},{"key":"ref_8","first-page":"200","article-title":"Neurotransmitters in CNS disease: dementia","volume":"ii:","author":"Rossor, M.N.","year":"1982","unstructured":"Rossor MN. Neurotransmitters in CNS disease: dementia. Lancer 1982;ii:200-4.","journal-title":"Lancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1126\/science.7058341","article-title":"Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain","volume":"215","author":"Whitehouse, P.J.; Price, D.L.; Struble, R.G.; Clark, A.W.; Coyle, J.T.; Delong, M.R.","year":"1982","unstructured":"Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delong MR. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 1982;215:1237-9.","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1126\/science.6338589","article-title":"Alzheimer's disease: a disorder of cortical cholinergic innervation","volume":"219","author":"Coyle, J.T.; Price, D.L.; DeLong, M.R.","year":"1983","unstructured":"Coyle JT, Price DL, DeLong MR. Alzheimer's disease: a disorder of cortical cholinergic innervation. Science 1983;219:1184-90.","journal-title":"Science"},{"key":"ref_11","first-page":"1457","article-title":"Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med3'","volume":"ii:","author":"Perry, E.K.; Tomlinson, B.E.; Blessed, G.; Bergmann, K.; Gibson, P.H.; Perry, R.H.","year":"1978","unstructured":"Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med3' 1978;ii:1457-9."},{"key":"ref_12","first-page":"11","article-title":"Accelerated ageing or selective neuronal loss as an important cause of dementia","volume":"ii:","author":"Bowen, D.M.; Spillane, J.A.; Curzon, G.","year":"1979","unstructured":"Bowen DM, Spillane JA, Curzon G, et al. Accelerated ageing or selective neuronal loss as an important cause of dementia. Lancet 1979;ii:11-4.","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/0006-8993(79)90336-6","article-title":"Neurotransmitter-related enzymes in senile dementia of the Alzheimer type","volume":"171","author":"P, X3 Davies","year":"1979","unstructured":"X3 Davies P. Neurotransmitter-related enzymes in senile dementia of the Alzheimer type. Brain Res 1979;171:319-27.","journal-title":"Brain Res"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/brain\/105.2.313","article-title":"A post-mortem study of the cholinergic and GABA systems in senile dementia","volume":"105","author":"Rossor, M.N.; Garrett, N.J.; Johnson, A.L.; Mountjoy, C.Q.; Roth, M.; Iversen, L.L.","year":"1982","unstructured":"Rossor MN, Garrett NJ, Johnson AL, Mountjoy CQ, Roth M, Iversen LL. A post-mortem study of the cholinergic and GABA systems in senile dementia. Brain 1982;105:313-30.","journal-title":"Brain"},{"key":"ref_15","article-title":"The cholinergic defect of the frontal cortex in Alzheimer's disease is age dependent","author":"Rossor, M.N.; Iversen, L.L.; Johnson, A.L.; Mountjoy, C.Q.; Roth, M.","year":"1981","unstructured":"Rossor MN, Iversen LL, Johnson AL, Mountjoy CQ, Roth M. The cholinergic defect of the frontal cortex in Alzheimer's disease is age dependent. Lancet 1981;ii:1422.","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1192\/bjp.135.3.216","article-title":"Changes in brain catecholamines in patients with dementia of Alzheimer type","volume":"135","author":"Adolfsson, R.; Gottfries, C.G.; Roos, B.E.; Winblad, B.","year":"1979","unstructured":"Adolfsson R, Gottfries CG, Roos BE, Winblad B. Changes in brain catecholamines in patients with dementia of Alzheimer type. Br 7 Psychiatry 1979;135:216-23.","journal-title":"Br 7 Psychiatry"},{"key":"ref_17","first-page":"93","article-title":"Reduced dopamine-4-hydroxylase activity in Alzheimer's disease. Br MedJ7","volume":"282","year":"1981","unstructured":"Reduced dopamine-4-hydroxylase activity in Alzheimer's disease. Br MedJ7 1981;282:93-4."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1212\/WNL.32.2.164","article-title":"Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia","volume":"32","author":"Bondareff, W.; Mountjoy, C.Q.; Roth, M.","year":"1982","unstructured":"Bondareff W, Mountjoy CQ, Roth M. Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Neurology 1982;32:164-8.","journal-title":"Neurology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/ana.410100209","article-title":"Some morphometric aspects of the brain in senile dementia of the Alzheimer type","volume":"10","author":"Terry, R.D.; Peck, A.; De Teresa, R.; Schechter, R.; Horoupian, D.S.","year":"1981","unstructured":"Terry RD, Peck A, De Teresa R, Schechter R, Horoupian DS. Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol 1981;10:184-92.","journal-title":"Ann Neurol"},{"key":"ref_20","first-page":"439","article-title":"Psychological test performance in patients over sixty. I. Senile psychosis and the affective disorders of old age. 7ournal of Mental","volume":"99","author":"Roth, M.; Hopkins, B.","year":"1953","unstructured":"Roth M, Hopkins B. Psychological test performance in patients over sixty. I. Senile psychosis and the affective disorders of old age. 7ournal of Mental Science 1953;99:439-50.","journal-title":"Science"},{"issue":"1969","key":"ref_21","first-page":"465","article-title":"Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities","volume":"7","author":"Fonnum, F.","unstructured":"' Fonnum F. Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities. Biochem 7 1969; 115:465-72.","journal-title":"Biochem"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1471-4159.1965.tb06768.x","article-title":"A further study of the distribution of y-aminobutyric acid between excitatory and inhibitory axons of the lobster","volume":"12","author":"Kravitz, E.A.; Potter, D.D.","year":"1965","unstructured":"Kravitz EA, Potter DD. A further study of the distribution of y-aminobutyric acid between excitatory and inhibitory axons of the lobster. J Nezurochem 1965;12:323-8.","journal-title":"J Nezurochem"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0021-9673(00)95496-7","article-title":"Optimized isocratic conditions for analysis of catecholamines by high-performance reversed phase paired ion chromatography with anperometric detection","volume":"153","author":"Moyer, T.P.; Jiang, N.S.","year":"1978","unstructured":"Moyer TP, Jiang NS. Optimized isocratic conditions for analysis of catecholamines by high-performance reversed phase paired ion chromatography with anperometric detection. J Chromatogr 1978;153:365-72.","journal-title":"J Chromatogr"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/000456327901600103","article-title":"Development and validation of a specific radioimmunoassay for somatostatin in human plasma","volume":"16","author":"Penman, E.; Wass, J.A.H.; Lund, A.","year":"1979","unstructured":"Penman E, Wass JAH, Lund A, et al. Development and validation of a specific radioimmunoassay for somatostatin in human plasma. Ann Clin Biochem 1979;16:15-25.","journal-title":"Ann Clin Biochem"},{"key":"ref_25","first-page":"432","article-title":"Statistical methods","author":"Snedecor, G.W.; Cochran, W.G.","year":"1967","unstructured":"Snedecor GW, Cochran WG. Statistical methods. 6th ed. Iowa: State University, 1967:432.","edition":"6th ed"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0304-3940(83)90171-4","article-title":"Loss of pigmented and dopamine-b-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer type","volume":"39","author":"Iversen, L.L.; Rossor, M.N.; Reynolds, G.P.","year":"1983","unstructured":"Iversen LL, Rossor MN, Reynolds GP, et al. Loss of pigmented and dopamine-b-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer type. Neurosci Lett 1983;39:95-100.","journal-title":"Neurosci Lett"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/BF00687457","article-title":"The cerebral cortex in presenile dementia: a quantitative analysis","volume":"23","author":"Colon, E.J.","year":"1973","unstructured":"Colon EJ. The cerebral cortex in presenile dementia: a quantitative analysis. Acta Neuropathol (Berl) 1973;23:281-90.","journal-title":"Acta Neuropathol (Berl)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/288279a0","article-title":"Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer's disease and Alzheimer senile dementia","volume":"288","author":"Davies, P.; Katzman, R.; Terry, R.D.","year":"1980","unstructured":"Davies P, Katzman R, Terry RD. Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer's disease and Alzheimer senile dementia. Nature 1980;288:279-80.","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0304-3940(80)90177-9","article-title":"Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer type","volume":"20","author":"Rossor, M.N.; Emson, P.C.; Mountjoy, C.Q.; Roth, M.; Iversen, L.L.","year":"1980","unstructured":"Rossor MN, Emson PC, Mountjoy CQ, Roth M, Iversen LL. Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer type. Neurosci Lett 1980;20:373-7.","journal-title":"Neurosci Lett"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/brain\/102.2.333","article-title":"An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase and choline acetylase in human post-mortem brain tissue","volume":"102","author":"Spokes, E.G.S.","year":"1979","unstructured":"Spokes EGS. An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase and choline acetylase in human post-mortem brain tissue. Brain 1979;102:333-46.","journal-title":"Brain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/S0140-6736(83)92396-6","article-title":"Age and Alzheimer disease","volume":"i:","author":"Bondareff, W.","year":"1983","unstructured":"Bondareff W. Age and Alzheimer disease. Lancet 1983;i:1447.","journal-title":"Lancet"},{"key":"ref_32","author":"Accepted 19 J7anuary 1984)","unstructured":"(Accepted 19 J7anuary 1984)"}],"container-title":["BMJ"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/data.bmj.org\/tdm\/10.1136\/bmj.288.6422.961","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmj.288.6422.961","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T20:31:52Z","timestamp":1765398712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.bmj.com\/lookup\/doi\/10.1136\/bmj.288.6422.961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,3,31]]},"references-count":32,"journal-issue":{"issue":"6422","published-online":{"date-parts":[[1984,3,31]]},"published-print":{"date-parts":[[1984,3,31]]}},"alternative-id":["10.1136\/bmj.288.6422.961"],"URL":"https:\/\/doi.org\/10.1136\/bmj.288.6422.961","relation":{},"ISSN":["0007-1447","1468-5833"],"issn-type":[{"value":"0007-1447","type":"print"},{"value":"1468-5833","type":"electronic"}],"subject":[],"published":{"date-parts":[[1984,3,31]]}}}