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ALZHEIMER'S DISEASE AND ACETYLCHOLINESTERASE-CONTAINING NEURONS
513
Creutzfeldt-Jakob disease. The clinical picture was consistent with this diagnosis but the absence of myoclonus and the periodic EEG 1 changes are atypical.’ After full discussion with the patient’s relatives acyclovir was tried at a dose of 10 mg/kg thrice daily intravenously. No side-effects or complications were noted. The patient’s condition did not change. Nor did the EEG. The patient was transferred back to a psychiatric institution, where she died 4 weeks later. Creutzfeldt-Jakob disease (subacute spongiform encephalopathy) is caused by a transmissible agent, assumed to be a virus but as yet Antiviral unidentified. including amantadine,2,3 agents, vidarabine,4 and interferon5have been given with little or, at best, unconfirmed success. Acyclovir,like vidarabine, inhibits. DNA virus replication but is more potent. It was not effective in this case of Creutzfeldt-Jakob disease, where it was tried late in the illness. Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF
ANTHONY S. DAVID ROBERT GRANT JOHN P. BALLANTYNE
ALZHEIMER’S DISEASE AND
ACETYLCHOLINESTERASE-CONTAINING NEURONS
SIR,—The report by Averbackis noteworthy because it adds two further sites, the adrenal medulla and the anterior olfactory nucleus, to others in the nervous system where lesions are found in dementia of the Alzheimer type. However, we suggest that these findings do not reflect the "diffuse degenerative"7 nature of the disease, but rather may be a clue to its origin. The five cell groups outside the cortex where lesions occur all share a common feature: the cells contain acetylcholinesterase (AChE; see table). Only two of these cell groups are cholinergic, as defined by the presence of choline acetyltransferase (the nucleus basalis8and the anterior olfactory nucleus9). It is possible, therefore, that the disease is not specifically related to the central cholinergic system, but is connected with an abnormality of some of the cells that contain a particular isoenzyme of AChE-ie, the secretory isoenzyme that is present in CSF10 and which is reduced in amount in tissuesll and CSF12 from patients with Alzheimer’s disease. If the lesions in the adrenal medulla are really related to the disease, then this abnormality might be a primary one that iscoupled in some way to the presence of AChE. Alternatively, in the brain the AChE-containing cells might be affected as a result of retrograde changes following primary lesions in the telencephalon. 13 Our suggestion is in keeping with the idea that certain centralnervous-system diseases might be related to primary or secondary changes in neurons that constitute the isodendritic core of the brain,s and in this context it is striking that Parkinson’s disease affects another of the cell groups (substantia nigra pars compacta) 1. Roos R,
Gajdusek DC, Gibbs CJ. The clinical characteristics of transmissible Creutzfeldt-Jakob disease. Brain 1973; 96: 1-20. 2. Sanders WL. Creutzfeldt-Jakob disease treated with amantadine. J Neurol Neurosurg Psychiat 1979; 42: 960-61. 3. Terzano MG, Montonari E, Calzetti S, Mancia D, Lechi A. The effect of amantadine on arousal and EEG patterns in Creutzfeldt-Jakob disease. Arch Neurol 1983; 40: 555-59. 4. Furlow
TW, Whitley RJ, Wilmes FJ. Repeated suppression of Creutzfeldt-Jakob disease with vidarabine. Lancet 1982; ii: 564-65. 5. Kovanen J, Haltia M, Cantell K. Failure of interferon to modify Creutzfeldt-Jakob disease. Br Med J 1980; 280: 902. 6. Timbury MC. Acyclovir. Br Med J 1982; 285: 1223-24. 7. Averback P. Two new lesions in Alzheimer’s disease. Lancet 1983; ii: 1203. 8. Rossor MN. Dementia. Lancet 1982; ii: 1200-04. 9. Cuello AC, Sofroniew MV. The anatomy of the CNS cholinergic neurones. Trends Neurosci (in press). 10. Greenfield SA, Smith AD. The influence of electrical stimulation of certain brain areas on the concentration ofacetylcholinesterase in rabbit cerebrospinal fluid. Brain Res 1979; 177: 445-59. 11 Atack JR, Perry EK, Bonham JR, Perry RH, Tomlinson BE, Blessed G, Fairbairn A. Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: Selective loss of the intermediate (10S) form. Neurosci Lett 1983; 40: 199-204. 12. Appleyard ME, Smith AD, Wilcock GK, Esiri MM. Decreased CSF acetylcholinesterase activity in Alzheimer’s disease. Lancet 1983; ii: 452. 13. Pearson RCA, Sofroniew MV, Cuello AC, Powell TPS, Esiri MM, Wilcock GK. Persistence of cholinergic neurones in the basal nucleus in a brain with senile dementia of the Alzheimer type demonstrated by immunohistochemical staining for choline acetyltransferase. Brain Res 1983; 289: 375-79.
AChE-CONTAINING CELLS
AND ALZHEIMER’S DISEASE
The numbers tn the AChE column refer to references. The presence ofAChE within cells of the different cell groups has been shown so far mamly by histochemical studies in animals. *Sofromew MV, Cuello AC (unpublished).
that contains the secretory isoenzyme of AChE14 and that the 15 Drager syndrome also affects cell groups that are rich in AChE.
Shy-
University Departments of Pharmacology and Human Anatomy, Oxford OX1 3QT
ATHEROSCLEROSIS,
A. D. SMITH A. C. CUELLO
THE EAR LOBE
CREASE, AND
CHROMOSOME 11 SIR,—Dr Nerup and his colleagues from the Steno Memorial Hospital report an association between extensive atherosclerosis and certain DNA restriction fragments from chromosome 11 (Feb 4, p 250). Other workers from the same hospital earlier reported an association between atherosclerosis and a diagonal ear lobe crease,1 an association recently reviewed and added to by Elliott.2 Neither association appears to be due to common relationships with conventional risk factors. Could the ear lobe and chromosome 11 have something in common? Department of Community Medicine, Guy’s Hospital Medical School,
R. J. JARRETT
London SE1 9RT
HAZARDS OF NON-PRESCRIPTION POTASSIUM SUPPLEMENTS
SIR,-I would like
to
add
a note
of caution
on
the
use
of
non-
prescription K supplements and Na + /K mixtures described by Neyses et a1.3 A 63-year-old man with cardiomyopathy taking frusemide 40 mg and spironolactone 100 mg daily maintained his serum K at 4-5 mmol/1 for several years. Then the serumK rose to 5 -4 mmol/1 with a normal blood-urea and serum creatinine. The spironolactone dose was reduced to 50 mg daily but the serum K+ then rose to 6’ 2 mmol/1 with normal blood-urea and mild metabolic acidosis. The patient admitted to using a K+ supplement (’No Salt’) which contained 35 mmol K+ per half teaspoon. When he stopped taking this product his serum K reverted to normal. Spironolactoneis associated with hyperkalaemia in 8’ 6% of patients and is more common in patients receiving K+ supplements (15-8%). 14. Cuello AC, Romero E, Smith AD. In vitro release of acetylcholinesterase from the rat substantia nigra. J Physiol (Lond) 1981; 312: 14P-15P. 15. Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system associated with autonomic failure. Brain 1975; 95: 457-74. 16. Levey AI, Wainer BH, Mufson EJ, Mesulam M-M. Co-localization of acetylcholinesterase and choline acetyltransferase in the rat cerebrum. Neuroscience 1983; 9: 9-22. 17. Knight DP. Histochemical demonstration of catecholamines and acetylcholine esterase in the same cell bodies in the locus coeruleus (rat hind brain). Proc Roy Microsc Soc
1970; 6: 26-27. 18. Koelle GB. Cytological distributions and physiological functions of cholinesterases. In: Koelle GB, ed. Cholinesterases and anticholinesterase agents. Berlin: Springer, 1963: 187-298.
neurofibrillary changes in the brain stem and hypothalamus of senile dementia Acta Neuropathol (Berlin) 1966; 6: 181-87. 20. Somogyi P, Chubb IW, Smith AD. A possible structural basis for the extracellular release of acetylcholinesterase. Proc Roy Soc B 1975; 191: 271-83. 1. Christiansen JS, Mathiesen B, Andersen AR, Calberg H. Diagonal ear-lobe crease in coronary heart disease. N Engl J Med 1975; 293: 308-09. 2. Elliott WJ. Ear lobe crease and coronary artery disease: 1000 patients and review of the literature Am J Med 1983; 75: 1024-32 3. Neyses L, Groth H, Velter W. Acceptability in food of NaCl/KCl mixture. Lancet 19. Ishii T. Disribution of Alzheimer’s
1983; ii: 427. 4. Greenblatt DJ, et al. Adverse reactions to
spironolactone. JAMA 1973;
226: 40-43.
Creutzfeldt-Jakob disease. The clinical picture was consistent with this diagnosis but the absence of myoclonus and the periodic EEG 1 changes are atypical.’ After full discussion with the patient’s relatives acyclovir was tried at a dose of 10 mg/kg thrice daily intravenously. No side-effects or complications were noted. The patient’s condition did not change. Nor did the EEG. The patient was transferred back to a psychiatric institution, where she died 4 weeks later. Creutzfeldt-Jakob disease (subacute spongiform encephalopathy) is caused by a transmissible agent, assumed to be a virus but as yet Antiviral unidentified. including amantadine,2,3 agents, vidarabine,4 and interferon5have been given with little or, at best, unconfirmed success. Acyclovir,like vidarabine, inhibits. DNA virus replication but is more potent. It was not effective in this case of Creutzfeldt-Jakob disease, where it was tried late in the illness. Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF
ANTHONY S. DAVID ROBERT GRANT JOHN P. BALLANTYNE
ALZHEIMER’S DISEASE AND
ACETYLCHOLINESTERASE-CONTAINING NEURONS
SIR,—The report by Averbackis noteworthy because it adds two further sites, the adrenal medulla and the anterior olfactory nucleus, to others in the nervous system where lesions are found in dementia of the Alzheimer type. However, we suggest that these findings do not reflect the "diffuse degenerative"7 nature of the disease, but rather may be a clue to its origin. The five cell groups outside the cortex where lesions occur all share a common feature: the cells contain acetylcholinesterase (AChE; see table). Only two of these cell groups are cholinergic, as defined by the presence of choline acetyltransferase (the nucleus basalis8and the anterior olfactory nucleus9). It is possible, therefore, that the disease is not specifically related to the central cholinergic system, but is connected with an abnormality of some of the cells that contain a particular isoenzyme of AChE-ie, the secretory isoenzyme that is present in CSF10 and which is reduced in amount in tissuesll and CSF12 from patients with Alzheimer’s disease. If the lesions in the adrenal medulla are really related to the disease, then this abnormality might be a primary one that iscoupled in some way to the presence of AChE. Alternatively, in the brain the AChE-containing cells might be affected as a result of retrograde changes following primary lesions in the telencephalon. 13 Our suggestion is in keeping with the idea that certain centralnervous-system diseases might be related to primary or secondary changes in neurons that constitute the isodendritic core of the brain,s and in this context it is striking that Parkinson’s disease affects another of the cell groups (substantia nigra pars compacta) 1. Roos R,
Gajdusek DC, Gibbs CJ. The clinical characteristics of transmissible Creutzfeldt-Jakob disease. Brain 1973; 96: 1-20. 2. Sanders WL. Creutzfeldt-Jakob disease treated with amantadine. J Neurol Neurosurg Psychiat 1979; 42: 960-61. 3. Terzano MG, Montonari E, Calzetti S, Mancia D, Lechi A. The effect of amantadine on arousal and EEG patterns in Creutzfeldt-Jakob disease. Arch Neurol 1983; 40: 555-59. 4. Furlow
TW, Whitley RJ, Wilmes FJ. Repeated suppression of Creutzfeldt-Jakob disease with vidarabine. Lancet 1982; ii: 564-65. 5. Kovanen J, Haltia M, Cantell K. Failure of interferon to modify Creutzfeldt-Jakob disease. Br Med J 1980; 280: 902. 6. Timbury MC. Acyclovir. Br Med J 1982; 285: 1223-24. 7. Averback P. Two new lesions in Alzheimer’s disease. Lancet 1983; ii: 1203. 8. Rossor MN. Dementia. Lancet 1982; ii: 1200-04. 9. Cuello AC, Sofroniew MV. The anatomy of the CNS cholinergic neurones. Trends Neurosci (in press). 10. Greenfield SA, Smith AD. The influence of electrical stimulation of certain brain areas on the concentration ofacetylcholinesterase in rabbit cerebrospinal fluid. Brain Res 1979; 177: 445-59. 11 Atack JR, Perry EK, Bonham JR, Perry RH, Tomlinson BE, Blessed G, Fairbairn A. Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: Selective loss of the intermediate (10S) form. Neurosci Lett 1983; 40: 199-204. 12. Appleyard ME, Smith AD, Wilcock GK, Esiri MM. Decreased CSF acetylcholinesterase activity in Alzheimer’s disease. Lancet 1983; ii: 452. 13. Pearson RCA, Sofroniew MV, Cuello AC, Powell TPS, Esiri MM, Wilcock GK. Persistence of cholinergic neurones in the basal nucleus in a brain with senile dementia of the Alzheimer type demonstrated by immunohistochemical staining for choline acetyltransferase. Brain Res 1983; 289: 375-79.
AChE-CONTAINING CELLS
AND ALZHEIMER’S DISEASE
The numbers tn the AChE column refer to references. The presence ofAChE within cells of the different cell groups has been shown so far mamly by histochemical studies in animals. *Sofromew MV, Cuello AC (unpublished).
that contains the secretory isoenzyme of AChE14 and that the 15 Drager syndrome also affects cell groups that are rich in AChE.
Shy-
University Departments of Pharmacology and Human Anatomy, Oxford OX1 3QT
ATHEROSCLEROSIS,
A. D. SMITH A. C. CUELLO
THE EAR LOBE
CREASE, AND
CHROMOSOME 11 SIR,—Dr Nerup and his colleagues from the Steno Memorial Hospital report an association between extensive atherosclerosis and certain DNA restriction fragments from chromosome 11 (Feb 4, p 250). Other workers from the same hospital earlier reported an association between atherosclerosis and a diagonal ear lobe crease,1 an association recently reviewed and added to by Elliott.2 Neither association appears to be due to common relationships with conventional risk factors. Could the ear lobe and chromosome 11 have something in common? Department of Community Medicine, Guy’s Hospital Medical School,
R. J. JARRETT
London SE1 9RT
HAZARDS OF NON-PRESCRIPTION POTASSIUM SUPPLEMENTS
SIR,-I would like
to
add
a note
of caution
on
the
use
of
non-
prescription K supplements and Na + /K mixtures described by Neyses et a1.3 A 63-year-old man with cardiomyopathy taking frusemide 40 mg and spironolactone 100 mg daily maintained his serum K at 4-5 mmol/1 for several years. Then the serumK rose to 5 -4 mmol/1 with a normal blood-urea and serum creatinine. The spironolactone dose was reduced to 50 mg daily but the serum K+ then rose to 6’ 2 mmol/1 with normal blood-urea and mild metabolic acidosis. The patient admitted to using a K+ supplement (’No Salt’) which contained 35 mmol K+ per half teaspoon. When he stopped taking this product his serum K reverted to normal. Spironolactoneis associated with hyperkalaemia in 8’ 6% of patients and is more common in patients receiving K+ supplements (15-8%). 14. Cuello AC, Romero E, Smith AD. In vitro release of acetylcholinesterase from the rat substantia nigra. J Physiol (Lond) 1981; 312: 14P-15P. 15. Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system associated with autonomic failure. Brain 1975; 95: 457-74. 16. Levey AI, Wainer BH, Mufson EJ, Mesulam M-M. Co-localization of acetylcholinesterase and choline acetyltransferase in the rat cerebrum. Neuroscience 1983; 9: 9-22. 17. Knight DP. Histochemical demonstration of catecholamines and acetylcholine esterase in the same cell bodies in the locus coeruleus (rat hind brain). Proc Roy Microsc Soc
1970; 6: 26-27. 18. Koelle GB. Cytological distributions and physiological functions of cholinesterases. In: Koelle GB, ed. Cholinesterases and anticholinesterase agents. Berlin: Springer, 1963: 187-298.
neurofibrillary changes in the brain stem and hypothalamus of senile dementia Acta Neuropathol (Berlin) 1966; 6: 181-87. 20. Somogyi P, Chubb IW, Smith AD. A possible structural basis for the extracellular release of acetylcholinesterase. Proc Roy Soc B 1975; 191: 271-83. 1. Christiansen JS, Mathiesen B, Andersen AR, Calberg H. Diagonal ear-lobe crease in coronary heart disease. N Engl J Med 1975; 293: 308-09. 2. Elliott WJ. Ear lobe crease and coronary artery disease: 1000 patients and review of the literature Am J Med 1983; 75: 1024-32 3. Neyses L, Groth H, Velter W. Acceptability in food of NaCl/KCl mixture. Lancet 19. Ishii T. Disribution of Alzheimer’s
1983; ii: 427. 4. Greenblatt DJ, et al. Adverse reactions to
spironolactone. JAMA 1973;
226: 40-43.