11. a quantitative morphological study on the human basomedial telencephalic magnocellular...

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improvements in the care and treatment of patients suffering from neuro- and psychogeriatric diseases, particularly primary degenerative dementia, i.e., pre- senile and senile dementia of Alzheimer's type (AD) and Parkinson's disease (PD). The complexity of the matter renders a multidisciplinary approach neces- sary. Within the team the following disciplines are represented: neuroanatomy, neurophysiology, bio- chemistry, pathology, neuropharmacology, neuro- psychology, psychiatry and clinical neurology. The research programme comprises the following three components: 1. Longitudinal investigations to be carried out on four carefully selected cohorts: a cohort of patients suffering from PD, one of patients in the initial phase of AD, one of patients in an advanced phase of AD and one of control persons. 2. A series of multidisci- plinary research projects in which the emphasis lays on the basic neurosciences (phase I projects}. 3. A series of multidisciplinary research projects to bc started in 1989 in which the emphasis will lay on the clinical neurosciences (phase II projects). The phase ! projects pursue the following goals: a. to obtain a clear picture of the structural, ultrastructural and biochemical changes in the brains of patients who have suffered from PD and AD, b. creation of sensi- tive diagnostic tests for AD: c. development of mo- dels of AD for testing the effectivity of pharmaca. We expect that combination of the knowledge and insights emanating from the phase I projects with the results from the clinical longitudinal investigations, will be conductive to an optimal formulation of the projects to be implemented in phase II. 10. A quantitative morphological study on some monoaminergic brainstem nuclei in the normal aged brain I.R.L.M. Miiskens, H.J. ten Donkelaar, R. Nieu- wenhuys and B.P.M. Schulte (Nijmegen, The Netherlands) Several studies have shown the occurrence of degene- rative changes (e.g., cell loss, decrease of nucleolar volume, neurofibrillary tangles, senile plaques, Lewy bodies) in several brainstem nuclei in aging diseases such as Alzheimer's disease and Parkinson's disease. Cell counts in the dopaminergic substantia nigra pars compacta and ventral tegmental area, the noradre- nergic locus coeruleus and the serotonergic dorsal raphe nucleus show a significant decline of cell num- ber, the latter apparently decreasing linearly with age between birth and aged to about 50% at the age of 60 (see, e.g., McGeer, Can. J. Physiol. Pharmacol. 1984,62:741; Tabaton et al. Acta Neuropath. 1985,68:218). In normal aging cell loss has been re- ported to occur in locus coeruleus and the substanta nigra. In many studies changes in cell number are based on one section only. To our knowledge the absolute cell number of the dorsal raphe nucleus has never been established satisfactorily. As part of a research pro- gram on aging and aging diseases degenerative chan- ges in Alzheimer's and Parkinson's disease are being studied. In order to achieve a normal reference for cell numbers in the involved nuclei in the aged brain the total cell number of the above mentioned nuclei will be determined in an aged brain using conventio- nal counting techniques and a non-biased stereologi- cal method. First results will be presented. 11. A quantitative morphological study on the human basomedial telencephalic magnoceilular celcontinuum (BTMC) in "normal" aging O.J.M. Vogels, H.J. ter Laak, R. Nieuwenhuys and B.P.M. Schulte (Nijmegen, The Netherlands) The BTMC is an irregularly shaped cellcontinuum in the basal forebrain. It can be subdivided into three cell masses: medial septal nucleus, diagonal band of Broca and nucleus basalis of Meynert. In the last decade many authors described the important path- ophysiological role of the BTMC, especially the nu- cleus basalis of Meynert, in aging diseases of the central nervous system viz. Alzheimer's disease (AD) and Parkinson's disease (PD), whereas the BTMC is less affected in "normal" aging. In varying degree all authors report a considerable loss of neurons in the nucleus basalis of Meynert, a decrease of neuronal density and of neuronal size (both for AD and PD, in which dementia often co-exists). However, one can question the reliability of these results, due to two facts: 1) the methods used are seriously biased by inappropriate application of stereological principles, and 2) the small amount of material per BTMC examined. In this study morphometric parameters of the BTMC in the right and left hemisphere within one "normal" aged human brain will be presented using unbiased stereological methods. These parameters include neuron member, neuron size and neuron density, and an appropriate volume estimation of the BTMC. Spe- cial attention will be paid to inhomogeneities of neu- ron density and neuron size within the BTMC and to indistinct boundaries of the medial septal nucleus.

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Page 1: 11. A quantitative morphological study on the human basomedial telencephalic magnocellular celcontinuum (BTMC) in “normal” aging

improvements in the care and treatment of patients suffering from neuro- and psychogeriatric diseases, particularly primary degenerative dementia, i.e., pre- senile and senile dementia of Alzheimer's type (AD) and Parkinson's disease (PD). The complexity of the matter renders a multidisciplinary approach neces- sary. Within the team the following disciplines are represented: neuroanatomy, neurophysiology, bio- chemistry, pathology, neuropharmacology, neuro- psychology, psychiatry and clinical neurology. The research programme comprises the following three components: 1. Longitudinal investigations to be carried out on four carefully selected cohorts: a cohort of patients suffering from PD, one of patients in the initial phase of AD, one of patients in an advanced phase of AD and one of control persons. 2. A series of multidisci-

plinary research projects in which the emphasis lays on the basic neurosciences (phase I projects}. 3. A series of multidisciplinary research projects to bc started in 1989 in which the emphasis will lay on the clinical neurosciences (phase II projects). The phase ! projects pursue the following goals: a. to obtain a clear picture of the structural, ultrastructural and biochemical changes in the brains of patients who have suffered from PD and AD, b. creation of sensi- tive diagnostic tests for AD: c. development of mo- dels of AD for testing the effectivity of pharmaca. We expect that combination of the knowledge and insights emanating from the phase I projects with the results from the clinical longitudinal investigations, will be conductive to an optimal formulation of the projects to be implemented in phase II.

10. A quantitative morphological study on some monoaminergic brainstem nuclei in the normal aged brain

I.R.L.M. Miiskens, H.J. ten Donkelaar, R. Nieu- wenhuys and B.P.M. Schulte (Nijmegen, The Netherlands)

Several studies have shown the occurrence of degene- rative changes (e.g., cell loss, decrease of nucleolar volume, neurofibrillary tangles, senile plaques, Lewy bodies) in several brainstem nuclei in aging diseases such as Alzheimer's disease and Parkinson's disease. Cell counts in the dopaminergic substantia nigra pars compacta and ventral tegmental area, the noradre- nergic locus coeruleus and the serotonergic dorsal raphe nucleus show a significant decline of cell num- ber, the latter apparently decreasing linearly with age between birth and aged to about 50% at the age of 60 (see, e.g., McGeer, Can. J. Physiol. Pharmacol.

1984,62:741; Tabaton et al. Acta Neuropath. 1985,68:218). In normal aging cell loss has been re- ported to occur in locus coeruleus and the substanta nigra. In many studies changes in cell number are based on one section only. To our knowledge the absolute cell number of the dorsal raphe nucleus has never been established satisfactorily. As part of a research pro- gram on aging and aging diseases degenerative chan- ges in Alzheimer's and Parkinson's disease are being studied. In order to achieve a normal reference for cell numbers in the involved nuclei in the aged brain the total cell number of the above mentioned nuclei will be determined in an aged brain using conventio- nal counting techniques and a non-biased stereologi- cal method. First results will be presented.

11. A quantitative morphological study on the human basomedial telencephalic magnoceilular celcontinuum (BTMC) in "normal" aging

O.J.M. Vogels, H.J. ter Laak, R. Nieuwenhuys and B.P.M. Schulte (Nijmegen, The Netherlands)

The BTMC is an irregularly shaped cellcontinuum in the basal forebrain. It can be subdivided into three cell masses: medial septal nucleus, diagonal band of Broca and nucleus basalis of Meynert. In the last decade many authors described the important path- ophysiological role of the BTMC, especially the nu- cleus basalis of Meynert, in aging diseases of the central nervous system viz. Alzheimer's disease (AD) and Parkinson's disease (PD), whereas the BTMC is less affected in "normal" aging. In varying degree all authors report a considerable loss of neurons in the nucleus basalis of Meynert, a decrease of neuronal density and of neuronal size

(both for AD and PD, in which dementia often co-exists). However, one can question the reliability of these results, due to two facts: 1) the methods used are seriously biased by inappropriate application of stereological principles, and 2) the small amount of material per BTMC examined. In this study morphometric parameters of the BTMC in the right and left hemisphere within one "normal" aged human brain will be presented using unbiased stereological methods. These parameters include neuron member, neuron size and neuron density, and an appropriate volume estimation of the BTMC. Spe- cial attention will be paid to inhomogeneities of neu- ron density and neuron size within the BTMC and to indistinct boundaries of the medial septal nucleus.