perspectives A briefsketchof Sovietneuroscience Konstantin Anokhin Social and cultural philosophy/n the guise of various forms of materialismhaslongbeenthe basison whichSovietscience(including neuroscience)is founded.Neuroscientificresearchdevelopedwithin a number of 'schools', each associated with the doctrine of their founders and concentratedin a few large cities. Currently, central governmental funding covers research within state neuroscience programmes.
sessions in psychiatry in 1951, psychology in 1952, and by the postwar campaign for Russian patriotism and against cosmopolitism in science, has for a long time hindered the movement of Soviet neuroscience towards integration with the traditions and approaches of Western neurology. It has also played a significant role in the development of peculiar features of neuroscience schools in the Soviet KonstantinAnokhinis Soviet neuroscience has a long and complicated Union. Unlike many scientific schools in the West, at theMolecular history, which has determined many of its present their counterparts in the USSR usually continued NeurobiologyGroup, facets. A major impact on early neuroscientific their existence after the decease of their founder, his AnokhinInstituteof research in Russia was exerted by I. M. Sechenov. theory often becoming an official doctrine to be NormalPhysiology, His essay An Attempt to Introduce Physiological developed by his disciples. However, because of USSRAcademyof Foundations in Psychic Processes (1863) (the title of such methodological and conceptual stability over a MedicalSciences, Moscow,USSR. which was banned and replaced by the more neutral number of generations, many schools accumulated Reflexes of the Brain) contained an ingenious a vast amount of data and valuable systematic attempt to explain and analyse conscious life in experience in the analysis of the brain and in terms of the functions of the nervous system. behavioural issues. At present, Soviet neuroscience still bears some Sechenov's ideas received immense public enthusiasm in Russia in the second half of the 19th features of these impacts. There is still relative century and layed down a materialistic tradition for isolation of the schools, though there is a noticeable studies of mental processes, which can be followed tendency towards loosening conceptual borders and in Pavlov's theory of 'higher nervous activity' and towards creating a more empirically oriented research environment. Interactions between difBekhterev's 'reflexology'. These tendencies received even further support ferent groups of neuroscientists are complicated by after 1917, when dialectical materialism became an the fact that, in spite of the large number of research official philosophy of Soviet science. In neuroscience groups in this field, there is no national Neurothis period started with revolutionary excitement in science Society in the USSR. To some extent this role psychology in the 1920s, when all existing schools is played by the National Physiological Society. of psychological thought came together in the Other separate societies are the Psychological search for a materialist psychology consistent with Society, the Society of Psychiatrists and NeuroMarxism, being probably dominated by Kornilov's pathologists, and the Society of Biochemistry and Pharmacology, which cover various other subfields 'reactology' and Vygotsky's 'historico-cultural psychology'. However, this decade of unpre- of neuroscience. The Physiological Society holds its cedented theoretical innovations soon ended with a congresses only every four years. They attract series of ideological discussions on 'reactology' in 1000-1500 scientists, with probably half the contrithe years 1930-1932, and with a decree in 1936 by butions relating to the field of neuroscience. There the Party Central Committee on 'pedagogical per- are also meetings on the 'Problems of higher versions', which has outlawed research based on nervous activity', traditionally held every few years mental testing and led to the complete disappear- and having 200-300 participants. A number of ance of several psychological schools in the USSR. other special meetings, conferences, symposia and Another field of neuroscience has been an object workshops are regularly organized by research of the attention of the ideological authorities. institutes and universities. Several journals such as Pavlov's doctrine of 'higher nervous activity' was The Pavlovian Journal of Higher Nervous Activity, based on the idea of the conditioned reflex as a Neurophysiology, Neurochemistry and Sensory Sys'molecule of the mind' and, although the author tems are devoted to the publication of neuroscience himself denied that it was married with Marxist articles. Most of the neuroscience research in the USSR is philosophy, the theory was adopted after his death as a scientific complement to dialectical materialism carried out in institutes of the USSR Academy of and Lenin's philosophical theory of reflection. Sciences, the USSR Academy of Medical Sciences, Ideological control over this field culminated in 1950 the Republican Academies of Sciences, the Ministry in the famous 'Joint Pavlovian Session' of the USSR of Health and to a much lesser extent by departAcademy of Sciences and the USSR Academy of ments in universities and medical schools. A distincMedical Sciences, which accused a number of tive feature of Soviet neuroscience is concentration scientists (Orbeli, Beritashvili and Anokhin among of the research in a few large cities. For example, out those most severely attacked) of adopting new of all contributions to the recent 28th meeting on approaches and deviating from Pavlov's teaching. the 'Problems of higher nervous activity' (1989), This session, followed by less well-known similar 53% were from Moscow, 32% from Leningrad, 5% TINS, Vol. 14, No. 6, 1991
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TABLE I. Some main institutes involved in neuroscience research in Moscow and Leningrad City
Institutes
Moscow
Institute of Higher Nervous Activity and Neurophysiology, AS Brain ResearchInstitute, AMS All-Union Centre of Mental Health, AMS Moscow State University Anokhin Institute of Normal Physiology,AMS Institute of General Pathologyand Pathological Physiology, AMS Institute of Pharmacology, AMS Institute of Psychology, AS Burdenko Institute of Neurosurgery,AMS Koltsov Institute of Developmental Biology, AS
Leningrad
Pavlov Institute of Physiology, AS Institute of Experimental Medicine, AMS Institute of Human Brain, AS Sechenov Institute of Evolutionary Physiology and Biochemistry, AS Bechterev Psychoneurological Institute, AMS Leningrad State University
Abbreviations: AMS, USSRAcademy of Medical Sciences; AS, USSRAcademy of Sciences.
from Kiev and 3% from Novosibirsk, leaving 7% for the rest of the country. Some institutes involved in neuroscience research in Moscow and Leningrad are listed in Table I. The main means of coordinating research between the institutes belonging to different departments has been a system of central planning and long-term state programmes regulated through a series of scientific councils. A major proportion of neuroscience research from 1978 to 1990 has been conducted under a programme called 'Brain', which was developed by the United Scientific Council on Physiological Sciences of the USSR Academy of Sciences. The programme involves 27 institutes belonging to the Academies of Sciences of the USSR and Republics, 13 institutes from the Academy of Medical Sciences, 30 institutes of the Ministries of Health of the USSR and Republics, 6 universities and 15 institutes belonging to other ministries and departments. Presently there exist two other state programmes that cover the field of neuroscience:
TABLE II. Distribution of research projects in the field 'Physiology of the nervous system' in the USSRin the period 1986-1990" Research project
Percentage distribution
Fundamental problems of brain physiology Mechanisms of conditioned reflex Mechanisms of memory Experimental pathology and therapy of animal higher nervous activity Systems basisof behaviour Genetics of higher nervous activity and instinctive behaviour Functional neurochemistry
36.5 18.6 4.0 6.0 23.0 4.3 7.6
* Taken from Bechtereva,N. P., ed. (1988) Physiological Sciences in the USSR, Nauka Press,Leningrad. 230
'Physiological basis of thought, emotions and human state' and 'Intracellular signalling'. An essential peculiarity of this organizational system has been the dissociation of scientific and financial coordination within the programmes. Science in the USSR is funded almost exclusively by the government but in different and independent ways. Each state programme can include research groups belonging to different institutions, but the financial support for these groups is determined by the decisions of their own academies and ministries. For example, the above-mentioned state programmes are funding research only in the Academies of Sciences of the USSR and Republics, although up to half of the projects are conducted by groups not belonging to these institutions and which are funded by other sources. Moreover, funding is received by the institutes, rather than by the groups carrying out the specific projects, and decisions of the institute authorities play an important role in the distribution of funds between these research groups. Widespread dissatisfaction with this method of funding has been the reason for a number of organizational changes in recent years. The most significant of these changes is probably the movement towards the Western system of having research grants that are evaluated by groups of experts. Both the grant system and the old 'institutional' funding scheme are presently operating, with the possibility of each individual group receiving funding from both its institute or university budget and by application for additional grants from the government, if the research is in one of those areas of priority being supported. This favourable transitional state is, however, counteracted by severe cuts in spending for fundamental research, the lack of currency for modern equipment, isotopes and chemicals, and the absence of neuroscience subjects among the areas of major medical priority in the state programmes (presently concentrated on virology, diabetes, atherosclerosis, addiction, AIDS and oncology). As a result, large cuts in the research positions in fundamental neuroscience and reorganization of some institutes are strong possibilities in the next few years. Despite these organizational and financial difficulties, Soviet neuroscience is maintaining first-rate research in a number of fields. Areas such as the analysis of the neural mechanisms of conditioning and other types of learning, neurophysiology (from human electrophysiology and neuronal recording in conscious animals to cellular and membrane electrophysiology), behavioural pharmacology, and neurochemistry, have made distinct advances. On the other hand, fields such as developmental neurobiology and neuroanatomy are presently rather under-represented. An approximate impression of the current directions of, and the emphases on, different areas of research can be obtained from studying the distribution of projects in the field of physiology of the nervous system in the period 1986-1990 (Table II). The recent social and political changes in the TINS, VoL 14, No. 6, 1991
......
....
USSR have permitted the resumption of lively exchange between Soviet and Western scientists. In neuroscience this is not yet as extensive as, for example, that between molecular biologists or immunologists, who speak a more common language. However, the long-term separation between brain research in the USSR and the West, which had led to the development of different traditions and approaches, might now turn out to benefit both sides. Western scientists can have a closer acquaintance with the experience of different Soviet schools in the field of 'higher nervous ac-
p e r s p e c t i v e s
on
disease
tivity'. Collaboration and research exchange visits have already started between a number of Soviet and Western neuroscience laboratories. It is probably relevant to remember in this respect that many Russian neuroscientists, such as Kovalevsky, Sechenov, Pavlov, Bekhterev, Vvedenskii, Samoilov and others worked in leading European physiological laboratories, and on their return founded their own original approaches to neuroscience. They thus established traditions of developing culturally alongside other countries, which we have an opportunity to renew today.
Hereditary cerebral hemorrhage with amyloidosis - Dutch type: its importance for Alzheimer research Joost Haan, John A. Hardy and Raymund A. C. Roos A/zheimer'sdiseaseis now commonly regardedas a form of 'amyloid encephalopathy'1~. Amy/old depotits in the cerebra/blood vessels and parenchyma consist mainly of a unique protein called amyloid protein (A~P), which has a molecular weight of 4 kDa and is 42 amino acids long. These deposits are thought to be of pathogenetic importance in A/zheimer'sdisease. Recently, therefore, attention has been focused on the process of turnover of the precursor of A~P to amyloid fibrils, and the deposition and persistence of A~P in this disease. The study of several other diseases with cerebra/A~P deposition can be informative in this respect, because they allow the comparison of different pathogenetic mechanisms that lead to this type of deposition. One of these diseases is hereditary cerebra/ hemorrhage with amy/oidosis- Dutch type (HCHWA-D), which is the subject of this review. In the early sixties, the familial occurrence of cerebral hemorrhages with an autosomal dominant transmission was recognized in two small, adjacent Dutch coastal villages, Katwijk and Scheveningen 7. The disease, known as hereditary cerebral hemorrhage with amyloidosis- Dutch type (HCHWA-D), is characterized by recurrent strokes and affects normotensive, middle-aged patients. About 50% of the patients die as a result of the first stroke and the remaining half suffers from recurrent strokes8'9. In 1980, extensive cerebral amyloid angiopathy was identified as the cause of the strokes 1°,1~. Subsequently, the amyloid deposits in the meningeal and cortical arterioles of HCHWA-D patients were shown to resemble amyloid that occurs in Alzheimer's disease; that is, the first 21 residues of the amino-terminus are identical, and immunological cross-reactivity exists with a synthetic peptide homologous to the first 28 resid,ues of the protein forming amyloid in Alzheimers disease~2. Soon afterwards, HCHWA-D was categorized as one of the 'cerebral l~-amyloid diseases'2. Neuropsychological examination of HCHWA-D patients surviving one or more strokes revealed cognitive dysfunction, which, in the majority of TINS, Vol. 14, No. 6, 1991
patients, was sufficiently severe to be diagnosed as dementia 13. Dementia was correlated with the number of focal lesions on computed tomography (CT) scans of the brain, suggesting the presence of 'multi-infarct (hemorrhage) dementia'. However, some patients also have a history of progressive cognitive decline, apparently unrelated to strokes9,13. CT and nuclear magnetic resonance (NMR) studies of HCHWA-D patients have revealed recent cerebral hemorrhages and infarcts, or remnants of them 14'15. Remarkably, diffuse white matter damage was also present, visible on CT and NMR images13-~5. These white matter lesions resemble the lesions seen in patients with sporadic cerebral amyloid angiopathy 16 and Alzheimer's disease17, and are probably caused by chronic ischemia due to amyloid-induced stenosis of arterioles to the white matter 15--17.
JoostHaanand EaymundA. C Roos areat the Deptof Neurology, University Hospital, POBox 9600, 2300RC Leiden, The Netherlands,and JohnA. Hardyis at the Deptof Biochemistry,St Mary's Hospital MedicalSchoo/, Universityof London, Norfolk Place, London 14/21PG,UK.
Neuropathology The main neuropathological findings in HCHWAD are remnants of old and recent strokes, amyloid deposition in small leptomeningeal arteries and cortical arterioles 8, and incomplete infarction of the cerebral white matter ~5. Parenchymal amyloid deposits in the form of plaques, without the typical dense central amyloid core (as found in most plaques in patients with Alzheimer's disease) have been described 12. Neurofibrillary tangles and dystrophic neurites have never been found 12 ' 18 ' 19 , suggesting that the neuronal population is not involved in amyloidogenesis or storage of amyloid, nor is it severely damaged by amyloid. The density of the parenchymal amyloid deposits in HCHWA-D is much lower than in Alzheimer's disease12'18,19. The neuropathological similarities (amyloid angiopathy, parenchymal amyloid deposits), but also the differences, between these two diseases raise several pertinent questions. Is the vascular system
© 1991,ElsevieSci r encePublishersLid,(UK) 0166-2236/91/$0200
231
sessions in psychiatry in 1951, psychology in 1952, and by the postwar campaign for Russian patriotism and against cosmopolitism in science, has for a long time hindered the movement of Soviet neuroscience towards integration with the traditions and approaches of Western neurology. It has also played a significant role in the development of peculiar features of neuroscience schools in the Soviet KonstantinAnokhinis Soviet neuroscience has a long and complicated Union. Unlike many scientific schools in the West, at theMolecular history, which has determined many of its present their counterparts in the USSR usually continued NeurobiologyGroup, facets. A major impact on early neuroscientific their existence after the decease of their founder, his AnokhinInstituteof research in Russia was exerted by I. M. Sechenov. theory often becoming an official doctrine to be NormalPhysiology, His essay An Attempt to Introduce Physiological developed by his disciples. However, because of USSRAcademyof Foundations in Psychic Processes (1863) (the title of such methodological and conceptual stability over a MedicalSciences, Moscow,USSR. which was banned and replaced by the more neutral number of generations, many schools accumulated Reflexes of the Brain) contained an ingenious a vast amount of data and valuable systematic attempt to explain and analyse conscious life in experience in the analysis of the brain and in terms of the functions of the nervous system. behavioural issues. At present, Soviet neuroscience still bears some Sechenov's ideas received immense public enthusiasm in Russia in the second half of the 19th features of these impacts. There is still relative century and layed down a materialistic tradition for isolation of the schools, though there is a noticeable studies of mental processes, which can be followed tendency towards loosening conceptual borders and in Pavlov's theory of 'higher nervous activity' and towards creating a more empirically oriented research environment. Interactions between difBekhterev's 'reflexology'. These tendencies received even further support ferent groups of neuroscientists are complicated by after 1917, when dialectical materialism became an the fact that, in spite of the large number of research official philosophy of Soviet science. In neuroscience groups in this field, there is no national Neurothis period started with revolutionary excitement in science Society in the USSR. To some extent this role psychology in the 1920s, when all existing schools is played by the National Physiological Society. of psychological thought came together in the Other separate societies are the Psychological search for a materialist psychology consistent with Society, the Society of Psychiatrists and NeuroMarxism, being probably dominated by Kornilov's pathologists, and the Society of Biochemistry and Pharmacology, which cover various other subfields 'reactology' and Vygotsky's 'historico-cultural psychology'. However, this decade of unpre- of neuroscience. The Physiological Society holds its cedented theoretical innovations soon ended with a congresses only every four years. They attract series of ideological discussions on 'reactology' in 1000-1500 scientists, with probably half the contrithe years 1930-1932, and with a decree in 1936 by butions relating to the field of neuroscience. There the Party Central Committee on 'pedagogical per- are also meetings on the 'Problems of higher versions', which has outlawed research based on nervous activity', traditionally held every few years mental testing and led to the complete disappear- and having 200-300 participants. A number of ance of several psychological schools in the USSR. other special meetings, conferences, symposia and Another field of neuroscience has been an object workshops are regularly organized by research of the attention of the ideological authorities. institutes and universities. Several journals such as Pavlov's doctrine of 'higher nervous activity' was The Pavlovian Journal of Higher Nervous Activity, based on the idea of the conditioned reflex as a Neurophysiology, Neurochemistry and Sensory Sys'molecule of the mind' and, although the author tems are devoted to the publication of neuroscience himself denied that it was married with Marxist articles. Most of the neuroscience research in the USSR is philosophy, the theory was adopted after his death as a scientific complement to dialectical materialism carried out in institutes of the USSR Academy of and Lenin's philosophical theory of reflection. Sciences, the USSR Academy of Medical Sciences, Ideological control over this field culminated in 1950 the Republican Academies of Sciences, the Ministry in the famous 'Joint Pavlovian Session' of the USSR of Health and to a much lesser extent by departAcademy of Sciences and the USSR Academy of ments in universities and medical schools. A distincMedical Sciences, which accused a number of tive feature of Soviet neuroscience is concentration scientists (Orbeli, Beritashvili and Anokhin among of the research in a few large cities. For example, out those most severely attacked) of adopting new of all contributions to the recent 28th meeting on approaches and deviating from Pavlov's teaching. the 'Problems of higher nervous activity' (1989), This session, followed by less well-known similar 53% were from Moscow, 32% from Leningrad, 5% TINS, Vol. 14, No. 6, 1991
© 1991.ElsevieSci r encePublishersLtd.(UK) 0166-2236/91/$02.00
229
TABLE I. Some main institutes involved in neuroscience research in Moscow and Leningrad City
Institutes
Moscow
Institute of Higher Nervous Activity and Neurophysiology, AS Brain ResearchInstitute, AMS All-Union Centre of Mental Health, AMS Moscow State University Anokhin Institute of Normal Physiology,AMS Institute of General Pathologyand Pathological Physiology, AMS Institute of Pharmacology, AMS Institute of Psychology, AS Burdenko Institute of Neurosurgery,AMS Koltsov Institute of Developmental Biology, AS
Leningrad
Pavlov Institute of Physiology, AS Institute of Experimental Medicine, AMS Institute of Human Brain, AS Sechenov Institute of Evolutionary Physiology and Biochemistry, AS Bechterev Psychoneurological Institute, AMS Leningrad State University
Abbreviations: AMS, USSRAcademy of Medical Sciences; AS, USSRAcademy of Sciences.
from Kiev and 3% from Novosibirsk, leaving 7% for the rest of the country. Some institutes involved in neuroscience research in Moscow and Leningrad are listed in Table I. The main means of coordinating research between the institutes belonging to different departments has been a system of central planning and long-term state programmes regulated through a series of scientific councils. A major proportion of neuroscience research from 1978 to 1990 has been conducted under a programme called 'Brain', which was developed by the United Scientific Council on Physiological Sciences of the USSR Academy of Sciences. The programme involves 27 institutes belonging to the Academies of Sciences of the USSR and Republics, 13 institutes from the Academy of Medical Sciences, 30 institutes of the Ministries of Health of the USSR and Republics, 6 universities and 15 institutes belonging to other ministries and departments. Presently there exist two other state programmes that cover the field of neuroscience:
TABLE II. Distribution of research projects in the field 'Physiology of the nervous system' in the USSRin the period 1986-1990" Research project
Percentage distribution
Fundamental problems of brain physiology Mechanisms of conditioned reflex Mechanisms of memory Experimental pathology and therapy of animal higher nervous activity Systems basisof behaviour Genetics of higher nervous activity and instinctive behaviour Functional neurochemistry
36.5 18.6 4.0 6.0 23.0 4.3 7.6
* Taken from Bechtereva,N. P., ed. (1988) Physiological Sciences in the USSR, Nauka Press,Leningrad. 230
'Physiological basis of thought, emotions and human state' and 'Intracellular signalling'. An essential peculiarity of this organizational system has been the dissociation of scientific and financial coordination within the programmes. Science in the USSR is funded almost exclusively by the government but in different and independent ways. Each state programme can include research groups belonging to different institutions, but the financial support for these groups is determined by the decisions of their own academies and ministries. For example, the above-mentioned state programmes are funding research only in the Academies of Sciences of the USSR and Republics, although up to half of the projects are conducted by groups not belonging to these institutions and which are funded by other sources. Moreover, funding is received by the institutes, rather than by the groups carrying out the specific projects, and decisions of the institute authorities play an important role in the distribution of funds between these research groups. Widespread dissatisfaction with this method of funding has been the reason for a number of organizational changes in recent years. The most significant of these changes is probably the movement towards the Western system of having research grants that are evaluated by groups of experts. Both the grant system and the old 'institutional' funding scheme are presently operating, with the possibility of each individual group receiving funding from both its institute or university budget and by application for additional grants from the government, if the research is in one of those areas of priority being supported. This favourable transitional state is, however, counteracted by severe cuts in spending for fundamental research, the lack of currency for modern equipment, isotopes and chemicals, and the absence of neuroscience subjects among the areas of major medical priority in the state programmes (presently concentrated on virology, diabetes, atherosclerosis, addiction, AIDS and oncology). As a result, large cuts in the research positions in fundamental neuroscience and reorganization of some institutes are strong possibilities in the next few years. Despite these organizational and financial difficulties, Soviet neuroscience is maintaining first-rate research in a number of fields. Areas such as the analysis of the neural mechanisms of conditioning and other types of learning, neurophysiology (from human electrophysiology and neuronal recording in conscious animals to cellular and membrane electrophysiology), behavioural pharmacology, and neurochemistry, have made distinct advances. On the other hand, fields such as developmental neurobiology and neuroanatomy are presently rather under-represented. An approximate impression of the current directions of, and the emphases on, different areas of research can be obtained from studying the distribution of projects in the field of physiology of the nervous system in the period 1986-1990 (Table II). The recent social and political changes in the TINS, VoL 14, No. 6, 1991
......
....
USSR have permitted the resumption of lively exchange between Soviet and Western scientists. In neuroscience this is not yet as extensive as, for example, that between molecular biologists or immunologists, who speak a more common language. However, the long-term separation between brain research in the USSR and the West, which had led to the development of different traditions and approaches, might now turn out to benefit both sides. Western scientists can have a closer acquaintance with the experience of different Soviet schools in the field of 'higher nervous ac-
p e r s p e c t i v e s
on
disease
tivity'. Collaboration and research exchange visits have already started between a number of Soviet and Western neuroscience laboratories. It is probably relevant to remember in this respect that many Russian neuroscientists, such as Kovalevsky, Sechenov, Pavlov, Bekhterev, Vvedenskii, Samoilov and others worked in leading European physiological laboratories, and on their return founded their own original approaches to neuroscience. They thus established traditions of developing culturally alongside other countries, which we have an opportunity to renew today.
Hereditary cerebral hemorrhage with amyloidosis - Dutch type: its importance for Alzheimer research Joost Haan, John A. Hardy and Raymund A. C. Roos A/zheimer'sdiseaseis now commonly regardedas a form of 'amyloid encephalopathy'1~. Amy/old depotits in the cerebra/blood vessels and parenchyma consist mainly of a unique protein called amyloid protein (A~P), which has a molecular weight of 4 kDa and is 42 amino acids long. These deposits are thought to be of pathogenetic importance in A/zheimer'sdisease. Recently, therefore, attention has been focused on the process of turnover of the precursor of A~P to amyloid fibrils, and the deposition and persistence of A~P in this disease. The study of several other diseases with cerebra/A~P deposition can be informative in this respect, because they allow the comparison of different pathogenetic mechanisms that lead to this type of deposition. One of these diseases is hereditary cerebra/ hemorrhage with amy/oidosis- Dutch type (HCHWA-D), which is the subject of this review. In the early sixties, the familial occurrence of cerebral hemorrhages with an autosomal dominant transmission was recognized in two small, adjacent Dutch coastal villages, Katwijk and Scheveningen 7. The disease, known as hereditary cerebral hemorrhage with amyloidosis- Dutch type (HCHWA-D), is characterized by recurrent strokes and affects normotensive, middle-aged patients. About 50% of the patients die as a result of the first stroke and the remaining half suffers from recurrent strokes8'9. In 1980, extensive cerebral amyloid angiopathy was identified as the cause of the strokes 1°,1~. Subsequently, the amyloid deposits in the meningeal and cortical arterioles of HCHWA-D patients were shown to resemble amyloid that occurs in Alzheimer's disease; that is, the first 21 residues of the amino-terminus are identical, and immunological cross-reactivity exists with a synthetic peptide homologous to the first 28 resid,ues of the protein forming amyloid in Alzheimers disease~2. Soon afterwards, HCHWA-D was categorized as one of the 'cerebral l~-amyloid diseases'2. Neuropsychological examination of HCHWA-D patients surviving one or more strokes revealed cognitive dysfunction, which, in the majority of TINS, Vol. 14, No. 6, 1991
patients, was sufficiently severe to be diagnosed as dementia 13. Dementia was correlated with the number of focal lesions on computed tomography (CT) scans of the brain, suggesting the presence of 'multi-infarct (hemorrhage) dementia'. However, some patients also have a history of progressive cognitive decline, apparently unrelated to strokes9,13. CT and nuclear magnetic resonance (NMR) studies of HCHWA-D patients have revealed recent cerebral hemorrhages and infarcts, or remnants of them 14'15. Remarkably, diffuse white matter damage was also present, visible on CT and NMR images13-~5. These white matter lesions resemble the lesions seen in patients with sporadic cerebral amyloid angiopathy 16 and Alzheimer's disease17, and are probably caused by chronic ischemia due to amyloid-induced stenosis of arterioles to the white matter 15--17.
JoostHaanand EaymundA. C Roos areat the Deptof Neurology, University Hospital, POBox 9600, 2300RC Leiden, The Netherlands,and JohnA. Hardyis at the Deptof Biochemistry,St Mary's Hospital MedicalSchoo/, Universityof London, Norfolk Place, London 14/21PG,UK.
Neuropathology The main neuropathological findings in HCHWAD are remnants of old and recent strokes, amyloid deposition in small leptomeningeal arteries and cortical arterioles 8, and incomplete infarction of the cerebral white matter ~5. Parenchymal amyloid deposits in the form of plaques, without the typical dense central amyloid core (as found in most plaques in patients with Alzheimer's disease) have been described 12. Neurofibrillary tangles and dystrophic neurites have never been found 12 ' 18 ' 19 , suggesting that the neuronal population is not involved in amyloidogenesis or storage of amyloid, nor is it severely damaged by amyloid. The density of the parenchymal amyloid deposits in HCHWA-D is much lower than in Alzheimer's disease12'18,19. The neuropathological similarities (amyloid angiopathy, parenchymal amyloid deposits), but also the differences, between these two diseases raise several pertinent questions. Is the vascular system
© 1991,ElsevieSci r encePublishersLid,(UK) 0166-2236/91/$0200
231
