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Cytoplasmic oligodendroglial inclusions in a patient with striatonigral degeneration, olivopontocerebellar atrophy and “atypical” pick's disease
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NEUROBIOLOGY OF AGING, VOLUME 1l, Its90 ABSTRACTS OF SECOND INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE NEUROPATHOLOGY/ALZHEIMER'S DISEASE IN DEVELOPMENTAL DISABILITIES
In this study we investigate the reaction of CNS tissue components to vascular amyloid infiltrating the perivascular neuropil in patients with Hereditary Cystatin C Amyloidosis. Brain Tissue specimens with perivascular depositions, varying from mild to severe, were stained by the following conventional stains: H..E., Congo red, Bielschowsky's and Palmgren's silver stains and PTAH. Sections were also immunostained with a panel of antibodies against cystatin C, neurofibrillary tangles, Tau, GFAP, neurofilament, beta-protein, a 1-antichymotrypsin, and macrophages. Preliminary results show no immunoreactivity of cystatin C amyloid deposits to Tau, beta-protein, d-anti chymotrypsin and neurofibrillary tangles. They also indicate that cystatin C deposition in the neuropil provokes less reaction of the surrounding tissue components than has been reported in perivascular beta-protein amyloid deposits in Alzheimer's disease (1). 1. M.C. Peers, M.B. Lenders, A. Delafossez, A. Delacourte and M. Mazzuca: Cortical angiopathy in Ahheimer's disease: the formation of dystrophic perivascular neurites is related to the exudation of amyloid fibrils from the pathological vessels. Virchows Archiv A: Pathol. Anat. 1988; 414; 15-20. 2. J.M. Rozenmuller, P. Eikelenboom, F.C. Stam, K. Beyreuther, and C.L. Masters: A4 protein in Alzheimer's disease: Primary and secondary cellular events in extracellular amyloid deposition. J. Neuropathol. Exp Neurol. 1989; 48; 674-691.
79 ThQ l~nlle olaoue: Prooosst for a classification and nomenclature.
~tn(J
me I all i u
] n
maerophages
or
in
t he
nc~lrop
L] C .
g~
c o n t r a s t , five of the 12 p a t i e n t s w i l h o u t Lewv b)dies or pale b o d i e s showed n
81
J.Ulrich and A.Probst, Neuropathological Division, Institute of Pathology, CH-4003 Basel, Switzerland. Immunohistological stains for the beta-protein (or A4 peptide), enzymehistochemistry for acetylohotinesterase and newly developped stains based on silver-iodide (Campbell et ai., 1987) demonstrate a much greater variability of sende plaques than was assumed before. The traditional methods including electron microscopy permitted to ~stinguish plaques consisting nearly exclusively of altered neurites ( neuritic" or "early') of altered neurltes plus an amyloid core (named "classical') and nearly exclusively of amyloid ('amyloid" or "burned out'). Close examination of the same traditionally stained sections and of those stained for components of the cytoSkeleton also allows to distinguish subclasses amon(I the three classes mentioned: Plaques without amyloid (Thioflavme negative) and without altered neurites (Plaques "A', Probst et al., 1987) and plaques resembling the classical plaques but which have no neurites with an obvious alteration. With the new techniques additional morphological types can be observed, which have i~ common that they consist of betaprotein (and possibly related substances) only, but do not show signs of gllat activitation, nor of cytoskelatat neuritic alteration. We suggest to name these "praplaques', those traditionally known "plaques'. As recent publications use very confusing and conflicting terminologies, we suggest researchers in the field should agree on a nomenclature, which we propose could be the following: Preplaques (amorphous deposits of beta-protein and possibly related substances): Subplal, diffuse, punctate, cotton wool-like, aggregates of punctate or cotton wool-like deposits. Plaque A (well delimited, central microgliai cell, astrocytic reaction, beta-protein deposits). Plaque B (neuritic changes, presence of microglla and reactive astrocytas, beta-protein deposits, some as amyoid whisps), formerly designated as neuritic plaques. Plaques C (as B, but with a central amyicid core), formady classical or mature. A subtype of Plaque C, formerly not distinguished from classical plaques, has no neuritic alterations (Plaques C'), Plaque D (Central amyloid core, surrounded by microglia and astrocytes, very little or no neuritic changes).
ROSTROCAUDAL INCREASE OF NEUROPATHOLOGIC DETERMIN A N T S IN T H E N U C L E U S BASALIS OF MEYNERT COMPLEX IN A L Z H E I M E R ' S DISEASE. "O.J.M. V o g e l s , C.A.J. Broere. K. R e n k e w e k . Institute of N e u r o l o g y , University of Nijmegen, P.O. Box 9101, 6500 HB N i j m e g e n , the N e t h e r l a n d s . S i g n i f i c a n t loss of magnoce]lular n e u r o n s in the n u c l e u s b a s a l l s of M e y n e r t c o m p l e x (NBMC) in A l z h e i m e r ' s d i s e a s e (AD) r a n g i n g from 50% to 90% has f r e q u e n t l y b e e n r e p o r t e d . Our s t u d y was p e r f o r m e d on b o t h h e m i s p h e r e s of i0 AD b r a i n s and 8 a g e - m a t c h e d c o n t r o l s , end in c l u d e d all cell sizes in the c o u n t i n g p r o c e d u r e , An o v e r a l l n e u r o n loss of only 15.5% for the w h o l e N B M C was found. W i t h i n the s u b d i v i s i o n s of the N B M C (Chl+Ch2, Ch3, Ch4a, Ch4i and Ch4p) total neuron loss varied from 0% rostrally (Chl+Ch2) up to 36% in the most c a u d a l part of the N B M C (Ch4p). A s i g n i f i c a n t i n c r e a s e in the n u m b e r of small-sized neurons and a s i g n i f i c a n t d e c r e a s e in the n u m b e r of l a r g e - s i z e d n e u r o n s was d e m o n s t r a t e d in e a c h N B M C - s u b d i v i s i o n , s u g g e s t i n g that instead of n e u r o n a l loss the s h r i n k a g e of n e u r o n s is the m a j o r n e u r o p a t h o l o g i c feature. No l e f t - r i g h t d i f f e r e n c e s were d e t e c t e d . U s i n g the c o n g o r e d method, the p r e s e n t study a l s o shows a r o s t r o c a u d a ] i n c r e a s e in the n u m b e r of senile plaques and n e u r o f i h r i I l a r y tangles (N/mm2), C h I + C h Z b e i n g the least and C h 4 p being the most affected. C o n g o p h i l i c a n g i o p a t h y is e v e n l y d i s t r i b u t e d a l o n g the N B M C These findings correspond to the recently reported rostrocaudal d e c r e a s e of m R N A levels in NBMC-neurons for nerve growth factor receptors (NGF r) and fit into the p r e s u m e d N G F s h o r t a g e in the n e o c o m t e x and hippocampus upon w h i c h the N B M C axons t e r m i n a t e .
8O NIGRAL LEWY BODY DEGENERATION AND ALZHEIMER'S D I S E A S E . * M a r c G. Reyes, F r a n c e s c o F a r a l d i , Raji C h a n d r a n , A n d r e V e r a n o . C o o k C o u n t y H o s p i t a l and R u s h A l z h e i m e r ' s Center, C h i c a g o , IL and D e p a r t m e n t of H u m a n A n a t o m y , U n i v e r s i t y of Turin, I t a l y H i s t o p a t h o l o g i c e x a m i n a t i o n of the pars c o m p a c t a of the s u b s t a n t i a n i g r a of 17 p a t i e n t s w i t h A l z h e i m e r ' s D i s e a s e s h o w e d Lewy b o d i e s in, n e a r or a w a y from c y t o p l a s m i c pale b o d i e s of n e u r o n a l cell b o d i e s in six p a t i e n t s or pale b o d i e s o n l y in one p a t i e n t , all of w h o m had n e u r o n a l loss, a s t r o c y t o s i s
82 CYTOPLASMIC OLIGODENDROGLIAL INCLUSIONS IN A PATIENT WITH STRIATONIGRAL DEGENERATION, OLIVOPONTOCEREBELLAR ATROPIdY AND "ATYPICAL" PICK'S DISEASE. *D.S. Horoupian, Neuropathology, Stanford University, Stanford, CA 94305 A 75 year old woman with Parkinsonlsm plus was found at autopsy to have severe striatonigral degeneration, mfld ollvopontocerebellar atrophy and Pick bodies mainly localized to the hippocampal formation and the nuclei of the basis pontis. There was no cortical atrophy o r gllosls. In addition, pale eosinophilic bodies measuring 8~ in
NEUROBIOLOGY OF AGING, VOLUME 1 l, 1990 ABSTRACTS OF SECOND INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE NEUROPATHOLOGY/ALZHEIMER'S DISEASE IN DEVELOPMENTAL DISABILITIES diameter were seen in certain areas of the brain. In the gray matter, they were located in the deeper layers of the cortex and in decreasing order of frequency they occurred in the pericentral gyri, insular cortex and parietal cortex and in striatum. In the white matter, they were present in the extreme and external capsules, pencil fibers of the striatum, internal capsule, subcortical pre- and postcortical white matter and rarely in the cerebellum. They were spherical, flame or crescent shaped and frequently occurred next to nuclei having features of oligodendroglia. They were ubiquinated and argyrophilic; often displaying a dark circumferential staining and paler center by both methods. They immunoreacted with anti-Leu-7 but not with anti-neurofilament, Alz-50, Tau-i and GFAP. These inclusions had to be distinguished from cortical Lewy bodies, Pick bodies and the non-specific ubiquinated bodies in the white matter of aged brains, mainly by their topographical distribution and immunostaining properties.
83 STABILITY OF DENDR/TIC EXTENT OF BASAL FOREBRAIN NEURONS IN ALZHEIMER'S DISEASE (AD). *D. G. Hood, S. B. Stechna and S. D. Hanks. Depts. of Neurology and Neurobiology & Anatomy, Univ. of Rochester Sch. of M e d . & Dent., Rochester, NY 14642. One study (Arendt et al., Neuroscience, 19: 1265-1278, 1986) has reported increases in cell body size and in dendritic extent in basal forebrain neurons in a group of young (55-68 years of age), short duration of illness (2-5 years) AD cases. In addition to studying a relatively unusual sample of AD cases, the method of neuron selection was biased by the omission of all cells with degenerative changes. Regardless of the reason for having obtained significantly increased cell body sizes in the AD cases, their sample of basal forebrain neurons did not represent the usual picture of shrunken neurons in AD. Thus, it seemed appropriate to reevaluate the question of dendritic changes in basal forebrain neurons in AD. From over 80 cases obtained through the Rochester Alzheimer's Disease Project (RADP) and from over an additional 30 control cases, 14 subjects were assigned to two groups (7 per group): 1) normal aged adults (mean 81.6 years, range 73-87 years), and 2) AID (mean 79.6 years, range 74-87 years). All cases in the latter group had a history of dementia which proved to be AID at autopsy. All cases in the normal aged group lacked a history of any neurological or psychiatric abnormality and showed no significant neuropathology at autopsy. Nine to fifteen neurons from each of three regions of the basal forebrain (Ch2, Ch4am, and Ch4al) were randomly selected for analysis from coded 200 Bm sections of Golgi-Cox stained tissue. Cell body size and degree of dendritic atrophy were not selection criteria. Camera lucida tracings of these cells were digitized and measured by an Apple II Plus microcomputer with attached graphics tablet. Analysis showed cell body shrinkage in the AD cases that was significant in Ch2 and Ch4al and that was not significant in Ch4am. In spite of the cell body shrinkage in the AD cases, the parameters of dendritic extent, total dendritic length, numbers of segments, and average segment length, were not different from the control cases. These data suggest that the cell body shrinkage seen here and in Nissl-stained tissue in AD is associated with loss of efferent projections to cerebral cortex and hippocampus, while the afferent input to the basal forebrain neurons remains intact. Supported by NIH grant AG 03644.
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method) results in suppression of the amyloid-like pattern and preservation of the strong NFT and NT staining. The pattern resembles that of tau protein immunocytochemistry. The dystrophic neurites of mature SP's obscured by dense amyloid-like deposits in CPS-I preparations, are now clearly discerned. NT's are unequivocally identified from normal neurites which remain unstained. All phases of NFT evolution are well demonstrated. The earliest, "pre-tangle" abnormalities (neurons with granular cytoplasm and perinuclear rings) are particularly prominent with the CPS-II technique. The procedure may be useful as a diagnostic tool. It defects every lesion described in the AD brain and is of special value for the electron microscopic study of the earliest cerebral lesions of aging and AD. Supported by a grant from the Ohio Department of Aging. 85 IN SITU HYBRIDIZATION REVEALS INCREASED MUSCARINIC RECEPTOR mRNA IN ALZHEIMER'S DISEASE TEMPORAL CORTEX ,1,2p.j. Harrison, iA.J.Barton, 3A.Najlerahim, 4B.MacDonald. 3R.C.A. Pearson. Depts.of iAnatomy and 2psychiatry, St. Mary's Hospital Medical School, London W2 IPG; 3Dept. of Biomedical Science, The University, Sheffield; 4Dept. of Neuropathology, Radcliffe Infirmary, Oxford, U.K. We have used quantitative in situ hybridization (ISHH) to estimate amounts of the mRNA coding for the muscarinic M1 receptor in Alzheimer's disease (AD) and control temporal cortex. I0> frozen sections from middle temporal gyrus of six pathologically proven cases of AD and seven neurologically normal controls were used, matched for age and autopsy delay. A [35S]-labelled oligonucleotide complementary to bases 1690 to 1719 of the sequence of Allard et al (N.A.R, 15,10604) was used. Hybridization conditions were as described elsewhere (P.J.H.& R.C.A.P., Pro$.Neurobiol. (in press). Specificity of probe was confirmed by a Northern blot which showed a single band of 2.7kb. Other controls were given by hybridization with a sense strand, and on RNase treated ~ections, both of which produced no significant signal. Hybridized sections were placed against autoradiographic film for 14 days. FLlm was analysed directly with computerised image analysis by sampling through the depth of the grey matter, producing a mean optical density proportional to the strength of hybridization. Data was analysed blind to diagnosis. AD cases had a 270% increased hybridization signal compared to normal controls (p<0.05). This increase was gene-specific, in that total poly[Al+mRNA levels, as determined in a similar way using a probe directed against poly[A] tails, did not vary between the groups. We conclude that muscarinic receptor mRNA is up-regulated in AD temporal cortex, probably as a result of presynaptic cholinergic loss. The data also demonstrate the ability of ISHH to determine variation in lew~is as well as distribution of mRNAs. Further work will assess whether this increase is disease specific, and will relate signal strength to mRNA quantities at a regional and cellular level.
86 84 A HIGHLY SENSITIVE SILVER METHOD RESULTS IN HIGH CONTRAST AND FINE DELINEATION OF THE EARLIEST LESIONS OF ALZHEIMER'S DISEASE. ANALOGOUS PA]-IERN OF STAINING TO THAT OF TAU AND 6-AMYLOID PROTEIN IMMUNOCY'FOCHEMISTRY. *M.E. Velasco. Medical College of Ohio, Toledo, OH, 43699 USA. The treatment with copper-peroxide before ammoniacal silver results in enhanced argyrophylia of Alzheimer disease (AD) lesions and suppression of the natural argyrophylia of normal neurites. This copper-peroxide-silver(CPS) method produces specific, high contrast staining and crisp delineation of the thinnest fibrillary tangles (NFT's) and neuropil threads (NT's). No normal neurites are impregnated. The CPS-I procedure reveals identical numbers and types of amyloid deposits that 6-protein antibodies. These include conventional SP's, cerebrovascular amyloid, subpial deposits, large prosubicular clusters, ependymal fibrillary tangles (Biondi rings) and diffuse (preamyloid) plaques. The latter shoe as meshworks of delicate intertwined black filaments rather than granules of amorphous material. They frequently envelop intact neurons and in the cerebellar cortex form a lattice of regularly oriented fibrils ending at right angles on the apical dendrites of Purkinje cells. The pattern suggest abnormal intracellular deposits localized in axon terminals. A variant of the basic procedure (CPS-II
CHOLINERGIC MARKERS IN ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE *K.W.Lange, M.N. Rossor, P. Jenner, C.D. Marsden Institute of Neurology and The National Hospital, London and King's College, University of London, U.K. Marked cholinergic deficits in the cortex and hippocampus have been shown in Alzheimer's disease (AD) and Parkinson's disease (PD). The present study examined choline acetyltransferase activity (CHAT) as well as muscarinic and nicotinic receptor binding in the brain in neuropathologically confirmed AD and PD. Brain tissue was obtained from the frontal cortex, temporal cortex and hippocampus of patients with AD, demented and non-demented patients with PD and control subjects without neurological or psychiatric diseases. Using membrane homogenates saturation analyses were performed for muscarinic receptors with [3H]-pirenzepine (M 1 receptors) and [3H]-AF-DX 116 (possibly M-2 receptors) and for nicotinic receptors with (-)-[aH]-nicotine. In addition to marked deficits in ChAT activity, the maximal densities of ['H]-AF-DX 116 and (-)-]3H]-nicotine binding sites were decreased in both cortex and hippocampus of patients with AD and demented and nondemented patients with PD. Maximal [~H]-pirenzepine binding in the cortex was unchanged in AD and increased in PD. Alterations of Ko values were not observed. The results suggest that nicotinic and muscarinic M-2 receptor
NEUROBIOLOGY OF AGING, VOLUME 1l, Its90 ABSTRACTS OF SECOND INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE NEUROPATHOLOGY/ALZHEIMER'S DISEASE IN DEVELOPMENTAL DISABILITIES
In this study we investigate the reaction of CNS tissue components to vascular amyloid infiltrating the perivascular neuropil in patients with Hereditary Cystatin C Amyloidosis. Brain Tissue specimens with perivascular depositions, varying from mild to severe, were stained by the following conventional stains: H..E., Congo red, Bielschowsky's and Palmgren's silver stains and PTAH. Sections were also immunostained with a panel of antibodies against cystatin C, neurofibrillary tangles, Tau, GFAP, neurofilament, beta-protein, a 1-antichymotrypsin, and macrophages. Preliminary results show no immunoreactivity of cystatin C amyloid deposits to Tau, beta-protein, d-anti chymotrypsin and neurofibrillary tangles. They also indicate that cystatin C deposition in the neuropil provokes less reaction of the surrounding tissue components than has been reported in perivascular beta-protein amyloid deposits in Alzheimer's disease (1). 1. M.C. Peers, M.B. Lenders, A. Delafossez, A. Delacourte and M. Mazzuca: Cortical angiopathy in Ahheimer's disease: the formation of dystrophic perivascular neurites is related to the exudation of amyloid fibrils from the pathological vessels. Virchows Archiv A: Pathol. Anat. 1988; 414; 15-20. 2. J.M. Rozenmuller, P. Eikelenboom, F.C. Stam, K. Beyreuther, and C.L. Masters: A4 protein in Alzheimer's disease: Primary and secondary cellular events in extracellular amyloid deposition. J. Neuropathol. Exp Neurol. 1989; 48; 674-691.
79 ThQ l~nlle olaoue: Prooosst for a classification and nomenclature.
~tn(J
me I all i u
] n
maerophages
or
in
t he
nc~lrop
L] C .
g~
c o n t r a s t , five of the 12 p a t i e n t s w i l h o u t Lewv b)dies or pale b o d i e s showed n
81
J.Ulrich and A.Probst, Neuropathological Division, Institute of Pathology, CH-4003 Basel, Switzerland. Immunohistological stains for the beta-protein (or A4 peptide), enzymehistochemistry for acetylohotinesterase and newly developped stains based on silver-iodide (Campbell et ai., 1987) demonstrate a much greater variability of sende plaques than was assumed before. The traditional methods including electron microscopy permitted to ~stinguish plaques consisting nearly exclusively of altered neurites ( neuritic" or "early') of altered neurltes plus an amyloid core (named "classical') and nearly exclusively of amyloid ('amyloid" or "burned out'). Close examination of the same traditionally stained sections and of those stained for components of the cytoSkeleton also allows to distinguish subclasses amon(I the three classes mentioned: Plaques without amyloid (Thioflavme negative) and without altered neurites (Plaques "A', Probst et al., 1987) and plaques resembling the classical plaques but which have no neurites with an obvious alteration. With the new techniques additional morphological types can be observed, which have i~ common that they consist of betaprotein (and possibly related substances) only, but do not show signs of gllat activitation, nor of cytoskelatat neuritic alteration. We suggest to name these "praplaques', those traditionally known "plaques'. As recent publications use very confusing and conflicting terminologies, we suggest researchers in the field should agree on a nomenclature, which we propose could be the following: Preplaques (amorphous deposits of beta-protein and possibly related substances): Subplal, diffuse, punctate, cotton wool-like, aggregates of punctate or cotton wool-like deposits. Plaque A (well delimited, central microgliai cell, astrocytic reaction, beta-protein deposits). Plaque B (neuritic changes, presence of microglla and reactive astrocytas, beta-protein deposits, some as amyoid whisps), formerly designated as neuritic plaques. Plaques C (as B, but with a central amyicid core), formady classical or mature. A subtype of Plaque C, formerly not distinguished from classical plaques, has no neuritic alterations (Plaques C'), Plaque D (Central amyloid core, surrounded by microglia and astrocytes, very little or no neuritic changes).
ROSTROCAUDAL INCREASE OF NEUROPATHOLOGIC DETERMIN A N T S IN T H E N U C L E U S BASALIS OF MEYNERT COMPLEX IN A L Z H E I M E R ' S DISEASE. "O.J.M. V o g e l s , C.A.J. Broere. K. R e n k e w e k . Institute of N e u r o l o g y , University of Nijmegen, P.O. Box 9101, 6500 HB N i j m e g e n , the N e t h e r l a n d s . S i g n i f i c a n t loss of magnoce]lular n e u r o n s in the n u c l e u s b a s a l l s of M e y n e r t c o m p l e x (NBMC) in A l z h e i m e r ' s d i s e a s e (AD) r a n g i n g from 50% to 90% has f r e q u e n t l y b e e n r e p o r t e d . Our s t u d y was p e r f o r m e d on b o t h h e m i s p h e r e s of i0 AD b r a i n s and 8 a g e - m a t c h e d c o n t r o l s , end in c l u d e d all cell sizes in the c o u n t i n g p r o c e d u r e , An o v e r a l l n e u r o n loss of only 15.5% for the w h o l e N B M C was found. W i t h i n the s u b d i v i s i o n s of the N B M C (Chl+Ch2, Ch3, Ch4a, Ch4i and Ch4p) total neuron loss varied from 0% rostrally (Chl+Ch2) up to 36% in the most c a u d a l part of the N B M C (Ch4p). A s i g n i f i c a n t i n c r e a s e in the n u m b e r of small-sized neurons and a s i g n i f i c a n t d e c r e a s e in the n u m b e r of l a r g e - s i z e d n e u r o n s was d e m o n s t r a t e d in e a c h N B M C - s u b d i v i s i o n , s u g g e s t i n g that instead of n e u r o n a l loss the s h r i n k a g e of n e u r o n s is the m a j o r n e u r o p a t h o l o g i c feature. No l e f t - r i g h t d i f f e r e n c e s were d e t e c t e d . U s i n g the c o n g o r e d method, the p r e s e n t study a l s o shows a r o s t r o c a u d a ] i n c r e a s e in the n u m b e r of senile plaques and n e u r o f i h r i I l a r y tangles (N/mm2), C h I + C h Z b e i n g the least and C h 4 p being the most affected. C o n g o p h i l i c a n g i o p a t h y is e v e n l y d i s t r i b u t e d a l o n g the N B M C These findings correspond to the recently reported rostrocaudal d e c r e a s e of m R N A levels in NBMC-neurons for nerve growth factor receptors (NGF r) and fit into the p r e s u m e d N G F s h o r t a g e in the n e o c o m t e x and hippocampus upon w h i c h the N B M C axons t e r m i n a t e .
8O NIGRAL LEWY BODY DEGENERATION AND ALZHEIMER'S D I S E A S E . * M a r c G. Reyes, F r a n c e s c o F a r a l d i , Raji C h a n d r a n , A n d r e V e r a n o . C o o k C o u n t y H o s p i t a l and R u s h A l z h e i m e r ' s Center, C h i c a g o , IL and D e p a r t m e n t of H u m a n A n a t o m y , U n i v e r s i t y of Turin, I t a l y H i s t o p a t h o l o g i c e x a m i n a t i o n of the pars c o m p a c t a of the s u b s t a n t i a n i g r a of 17 p a t i e n t s w i t h A l z h e i m e r ' s D i s e a s e s h o w e d Lewy b o d i e s in, n e a r or a w a y from c y t o p l a s m i c pale b o d i e s of n e u r o n a l cell b o d i e s in six p a t i e n t s or pale b o d i e s o n l y in one p a t i e n t , all of w h o m had n e u r o n a l loss, a s t r o c y t o s i s
82 CYTOPLASMIC OLIGODENDROGLIAL INCLUSIONS IN A PATIENT WITH STRIATONIGRAL DEGENERATION, OLIVOPONTOCEREBELLAR ATROPIdY AND "ATYPICAL" PICK'S DISEASE. *D.S. Horoupian, Neuropathology, Stanford University, Stanford, CA 94305 A 75 year old woman with Parkinsonlsm plus was found at autopsy to have severe striatonigral degeneration, mfld ollvopontocerebellar atrophy and Pick bodies mainly localized to the hippocampal formation and the nuclei of the basis pontis. There was no cortical atrophy o r gllosls. In addition, pale eosinophilic bodies measuring 8~ in
NEUROBIOLOGY OF AGING, VOLUME 1 l, 1990 ABSTRACTS OF SECOND INTERNATIONAL CONFERENCE ON ALZHEIMER'S DISEASE NEUROPATHOLOGY/ALZHEIMER'S DISEASE IN DEVELOPMENTAL DISABILITIES diameter were seen in certain areas of the brain. In the gray matter, they were located in the deeper layers of the cortex and in decreasing order of frequency they occurred in the pericentral gyri, insular cortex and parietal cortex and in striatum. In the white matter, they were present in the extreme and external capsules, pencil fibers of the striatum, internal capsule, subcortical pre- and postcortical white matter and rarely in the cerebellum. They were spherical, flame or crescent shaped and frequently occurred next to nuclei having features of oligodendroglia. They were ubiquinated and argyrophilic; often displaying a dark circumferential staining and paler center by both methods. They immunoreacted with anti-Leu-7 but not with anti-neurofilament, Alz-50, Tau-i and GFAP. These inclusions had to be distinguished from cortical Lewy bodies, Pick bodies and the non-specific ubiquinated bodies in the white matter of aged brains, mainly by their topographical distribution and immunostaining properties.
83 STABILITY OF DENDR/TIC EXTENT OF BASAL FOREBRAIN NEURONS IN ALZHEIMER'S DISEASE (AD). *D. G. Hood, S. B. Stechna and S. D. Hanks. Depts. of Neurology and Neurobiology & Anatomy, Univ. of Rochester Sch. of M e d . & Dent., Rochester, NY 14642. One study (Arendt et al., Neuroscience, 19: 1265-1278, 1986) has reported increases in cell body size and in dendritic extent in basal forebrain neurons in a group of young (55-68 years of age), short duration of illness (2-5 years) AD cases. In addition to studying a relatively unusual sample of AD cases, the method of neuron selection was biased by the omission of all cells with degenerative changes. Regardless of the reason for having obtained significantly increased cell body sizes in the AD cases, their sample of basal forebrain neurons did not represent the usual picture of shrunken neurons in AD. Thus, it seemed appropriate to reevaluate the question of dendritic changes in basal forebrain neurons in AD. From over 80 cases obtained through the Rochester Alzheimer's Disease Project (RADP) and from over an additional 30 control cases, 14 subjects were assigned to two groups (7 per group): 1) normal aged adults (mean 81.6 years, range 73-87 years), and 2) AID (mean 79.6 years, range 74-87 years). All cases in the latter group had a history of dementia which proved to be AID at autopsy. All cases in the normal aged group lacked a history of any neurological or psychiatric abnormality and showed no significant neuropathology at autopsy. Nine to fifteen neurons from each of three regions of the basal forebrain (Ch2, Ch4am, and Ch4al) were randomly selected for analysis from coded 200 Bm sections of Golgi-Cox stained tissue. Cell body size and degree of dendritic atrophy were not selection criteria. Camera lucida tracings of these cells were digitized and measured by an Apple II Plus microcomputer with attached graphics tablet. Analysis showed cell body shrinkage in the AD cases that was significant in Ch2 and Ch4al and that was not significant in Ch4am. In spite of the cell body shrinkage in the AD cases, the parameters of dendritic extent, total dendritic length, numbers of segments, and average segment length, were not different from the control cases. These data suggest that the cell body shrinkage seen here and in Nissl-stained tissue in AD is associated with loss of efferent projections to cerebral cortex and hippocampus, while the afferent input to the basal forebrain neurons remains intact. Supported by NIH grant AG 03644.
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method) results in suppression of the amyloid-like pattern and preservation of the strong NFT and NT staining. The pattern resembles that of tau protein immunocytochemistry. The dystrophic neurites of mature SP's obscured by dense amyloid-like deposits in CPS-I preparations, are now clearly discerned. NT's are unequivocally identified from normal neurites which remain unstained. All phases of NFT evolution are well demonstrated. The earliest, "pre-tangle" abnormalities (neurons with granular cytoplasm and perinuclear rings) are particularly prominent with the CPS-II technique. The procedure may be useful as a diagnostic tool. It defects every lesion described in the AD brain and is of special value for the electron microscopic study of the earliest cerebral lesions of aging and AD. Supported by a grant from the Ohio Department of Aging. 85 IN SITU HYBRIDIZATION REVEALS INCREASED MUSCARINIC RECEPTOR mRNA IN ALZHEIMER'S DISEASE TEMPORAL CORTEX ,1,2p.j. Harrison, iA.J.Barton, 3A.Najlerahim, 4B.MacDonald. 3R.C.A. Pearson. Depts.of iAnatomy and 2psychiatry, St. Mary's Hospital Medical School, London W2 IPG; 3Dept. of Biomedical Science, The University, Sheffield; 4Dept. of Neuropathology, Radcliffe Infirmary, Oxford, U.K. We have used quantitative in situ hybridization (ISHH) to estimate amounts of the mRNA coding for the muscarinic M1 receptor in Alzheimer's disease (AD) and control temporal cortex. I0> frozen sections from middle temporal gyrus of six pathologically proven cases of AD and seven neurologically normal controls were used, matched for age and autopsy delay. A [35S]-labelled oligonucleotide complementary to bases 1690 to 1719 of the sequence of Allard et al (N.A.R, 15,10604) was used. Hybridization conditions were as described elsewhere (P.J.H.& R.C.A.P., Pro$.Neurobiol. (in press). Specificity of probe was confirmed by a Northern blot which showed a single band of 2.7kb. Other controls were given by hybridization with a sense strand, and on RNase treated ~ections, both of which produced no significant signal. Hybridized sections were placed against autoradiographic film for 14 days. FLlm was analysed directly with computerised image analysis by sampling through the depth of the grey matter, producing a mean optical density proportional to the strength of hybridization. Data was analysed blind to diagnosis. AD cases had a 270% increased hybridization signal compared to normal controls (p<0.05). This increase was gene-specific, in that total poly[Al+mRNA levels, as determined in a similar way using a probe directed against poly[A] tails, did not vary between the groups. We conclude that muscarinic receptor mRNA is up-regulated in AD temporal cortex, probably as a result of presynaptic cholinergic loss. The data also demonstrate the ability of ISHH to determine variation in lew~is as well as distribution of mRNAs. Further work will assess whether this increase is disease specific, and will relate signal strength to mRNA quantities at a regional and cellular level.
86 84 A HIGHLY SENSITIVE SILVER METHOD RESULTS IN HIGH CONTRAST AND FINE DELINEATION OF THE EARLIEST LESIONS OF ALZHEIMER'S DISEASE. ANALOGOUS PA]-IERN OF STAINING TO THAT OF TAU AND 6-AMYLOID PROTEIN IMMUNOCY'FOCHEMISTRY. *M.E. Velasco. Medical College of Ohio, Toledo, OH, 43699 USA. The treatment with copper-peroxide before ammoniacal silver results in enhanced argyrophylia of Alzheimer disease (AD) lesions and suppression of the natural argyrophylia of normal neurites. This copper-peroxide-silver(CPS) method produces specific, high contrast staining and crisp delineation of the thinnest fibrillary tangles (NFT's) and neuropil threads (NT's). No normal neurites are impregnated. The CPS-I procedure reveals identical numbers and types of amyloid deposits that 6-protein antibodies. These include conventional SP's, cerebrovascular amyloid, subpial deposits, large prosubicular clusters, ependymal fibrillary tangles (Biondi rings) and diffuse (preamyloid) plaques. The latter shoe as meshworks of delicate intertwined black filaments rather than granules of amorphous material. They frequently envelop intact neurons and in the cerebellar cortex form a lattice of regularly oriented fibrils ending at right angles on the apical dendrites of Purkinje cells. The pattern suggest abnormal intracellular deposits localized in axon terminals. A variant of the basic procedure (CPS-II
CHOLINERGIC MARKERS IN ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE *K.W.Lange, M.N. Rossor, P. Jenner, C.D. Marsden Institute of Neurology and The National Hospital, London and King's College, University of London, U.K. Marked cholinergic deficits in the cortex and hippocampus have been shown in Alzheimer's disease (AD) and Parkinson's disease (PD). The present study examined choline acetyltransferase activity (CHAT) as well as muscarinic and nicotinic receptor binding in the brain in neuropathologically confirmed AD and PD. Brain tissue was obtained from the frontal cortex, temporal cortex and hippocampus of patients with AD, demented and non-demented patients with PD and control subjects without neurological or psychiatric diseases. Using membrane homogenates saturation analyses were performed for muscarinic receptors with [3H]-pirenzepine (M 1 receptors) and [3H]-AF-DX 116 (possibly M-2 receptors) and for nicotinic receptors with (-)-[aH]-nicotine. In addition to marked deficits in ChAT activity, the maximal densities of ['H]-AF-DX 116 and (-)-]3H]-nicotine binding sites were decreased in both cortex and hippocampus of patients with AD and demented and nondemented patients with PD. Maximal [~H]-pirenzepine binding in the cortex was unchanged in AD and increased in PD. Alterations of Ko values were not observed. The results suggest that nicotinic and muscarinic M-2 receptor