Distribution of basal ganglia lesions in Pick's disease with Pick bodies: A topographic neuropathological study of eight autopsy cases

The distribution of the basal ganglia lesions, including the amygdala, striatum, and pallidum, were investigated neuropathologically in eight Japanese autopsy cases of Pick's disease with Pick bodies. The lesions were classified as mild, moderate or severe. The degree and distribution of basal ganglia lesions in all eight cases were uniform: the amygdala showed severe to moderate lesions, the caudate nucleus and putamen showed moderate to mild lesions, and the pallidum showed mild lesions. Furthermore, the lesions in the amygdala were more prominent in the basolateral group than in the corticomedial group. In Pick's disease with Pick bodies, the degree and distribution of the lesions within the basal ganglia differs from those reported in both ‘Pick's disease without Pick bodies’ and corticobasal degeneration (CBD), in which severe lesions were present in the pallidum. These neuropathological findings may contribute to the morphological differential diagnosis among Pick's disease with Pick bodies, ‘Pick's disease without Pick bodies’, and CBD.     

Preservation of nigral neurons in Pick's disease with Pick bodies: a clinicopathological and morphometric study of five autopsy cases.

Many reports have described loss of neurons in the substantia nigra in Pick's disease (PiD). In those reports, however, "Pick's disease" includes PiD without Pick bodies (PB), and there is only limited data available on regional nigral pathology in PiD with PB. To elucidate the pathological changes of the substantia nigra in PiD with PB, we examined five cases and 12 age-matched controls by morphometry. The number and size of pigmented and nonpigmented neurons, as well as the area of the substantia nigra were examined. The area of the substantia nigra was significantly reduced in PiD with PB. The pigmented and nonpigmented neuron counts in PiD with PB were not statistically different from those in controls. There was a significant reduction in the size of pigmented neurons in PiD with PB to 82% with that in the controls. In addition, after reviewing 48 cases of PiD with PB reported in the literature, we found that none of the cases with typical frontotemporal lobe symptoms exhibited parkinsonism until the terminal stage. These data are useful for discriminating PiD with PB from other diseases showing frontotemporal characteristics, including the frontal lobe degeneration type and the motor neuron disease type of frontotemporal dementia.     

Distribution of basal ganglia lesions in generalized variant of Pick's disease: a clinicopathological study of four autopsy cases

We investigated four Japanese autopsy cases of the generalized variant of Pick's disease ("basophilic inclusion body disease") both clinically and pathologically, and examined the degree and distribution of the basal ganglia lesions, including the amygdala, striatum, pallidum, and substantia nigra. The lesions in the amygdala, striatum, and pallidum were classified into three categories (slight, moderate, and severe). The lesions in the substantia nigra were qualitatively judged, compared with normal controls. Extrapyramidal signs, not noticed in the generalized variant of Pick's disease, were evident in all four cases, in addition to dementia. The degree and distribution of basal ganglia lesions in all four cases were uniform: the caudate nucleus showed severe lesions, the amygdala and putamen severe to moderate lesions, and the pallidum moderate to slight lesions. The substantia nigra in all our cases showed prominent neuronal loss, probably being one of the lesions responsible for extrapyramidal signs. In the generalized variant of Pick's disease, the degree and distribution of the alterations within the basal ganglia differs from those reported in Pick's disease with Pick bodies (PDPB) and corticobasal degeneration (CBD). In PDPB, severe lesions are present in the amygdala with relative sparing of the substantia nigra, compatible with rare extrapyramidal signs in PDPB, while in CBD, severe lesions are found in the pallidum and substantia nigra. These clinicopathological findings may contribute not only to the elucidation of clinicopathological hallmarks, but also to the progress of neuroimaging, in the generalized variant of Pick's disease.     

Distribution of cerebral cortical lesions in diffuse neurofibrillary tangles with calcification: a clinicopathological study of four autopsy cases showing prominent parietal lobe involvement

We investigated clinicopathologically four Japanese autopsy cases of diffuse neurofibrillary tangles with calcification (DNTC), which has been believed to be characterized by temporal or temporofrontal circumscribed lobar atrophy, and examined the distribution of their cerebral cortical lesions using hemisphere specimens. The lesions were classified into three categories (slight, moderate, and severe). Severe lesions were present in the temporal lobes and insular gyri of all four cases, consistent with the studies reported to date. In contrast, severe lesions were encountered in the parietal lobe of case 1 and moderate lesions were found in the parietal lobes of cases 2–4. Furthermore, moderate lesions of the precentral gyrus were present in cases 2–4, and moderate lesions of the postcentral gyrus were encountered in all four cases. We postulate that the distribution of cerebral cortical lesions in DNTC is more widespread than previously assumed. Our data also indicate that the unusual clinical signs of DNTC reported by several Japanese researchers, including parietal signs such as apraxia and agnosia, are roughly consistent with the topographic distribution of cerebral cortical lesions in DNTC elucidated in this study.     

Distribution of cerebral cortical lesions in corticobasal degeneration: a clinicopathological study of five autopsy cases in Japan

We investigated five Japanese patients with autopsy-proven corticobasal degeneration (CBD) both clinically and pathologically, and examined the distribution of their cerebral cortical lesions in hemisphere specimens. The lesions were classified into three categories (slight, moderate and severe). Only two of our patients had clinical features considered to be typical of CBD. Severe lesions were present in the posterior portions of the frontal lobe, anterior to the precentral gyrus in two patients with the clinical diagnosis of CBD. By comparison, in two patients with clinically diagnosed frontal Pick’s disease, and one with the clinical diagnosis of progressive supranuclear palsy (PSP), severe lesions were seen in the anterior portions of the frontal lobe. The primary motor area of all five had mostly slight to moderate lesions. We postulate that the clinical features of CBD have a much wider spectrum than previously believed. Our data also indicate that the lesion responsible for limb-kinetic apraxia in CBD is in the premotor cortex. We suggest that when the anterior portions of the frontal lobe are damaged, the clinical picture mimics those of Pick’s disease and PSP. In addition, we consider that focal cerebral atrophy of CBD is multicentric. Received: 3 February 1997 / Revised: 14 April 1997 / Accepted: 2 May 1997     

Quantitative neuropathologic analysis of Pick's disease cases: cortical distribution of Pick bodies and coexistence with Alzheimer's disease

Pick's disease is characterized morphologically by severe atrophy of the frontal and temporal lobes and the presence in the cerebral cortex of degenerative neuronal lesions referred to as Pick bodies. In the present study, we analyzed the regional and laminar distribution of Pick bodies in a series of 16 Pick's disease cases. These distribution and density patterns were compared with those observed for neurofibrillary tangles in Alzheimer's disease. Very high densities of Pick bodies were observed Ammon's horn, subiculum, entorhinal cortex, and in the granule cell layer of the dentate gyrus. In the frontal and temporal neocortex, they were preferentially distributed in layers II and VI. All of the Pick's disease cases also exhibited neurofibrillary tangles in the frontal and temporal areas and in the hippocampal formation, with higher densities in layers II–III than in layers V–VI of the neocortical regions. Interestingly, this laminar distribution of neurofibrillary tangles was strikingly different from that observed in Alzheimer's disease cases, where they were more numerous in the infragranular layers than in the supragranular layers. In addition, a few Pick's disease cases also had cortical senile plaques. These results suggest that the presence of neurofibrillary tangles in Pick's disease may be more frequent than previously reported, and that Pick's disease and Alzheimer's disease may coexist in certain cases. The lesion distribution patterns suggest that different populations of cortical neurons are affected in Pick's and Alzheimer's diseases, and that alterations of select corticocortical and corticosubcortical projections may distinguish these forms of dementia. It is also possible that these two disorders share certain pathogenetic mechanisms, even though both display specific patterns of regional and neuronal vulner-ability to the degenerative processes.Supported by the Brookdale Foundation, and NIH grants AG06647, AG05138 and AG08802     

Striatopallidonigral degeneration in Pick's disease: a clinicopathological study of 41 cases

Summary The frequency and degree of stiatopallidonigral (SPN) degeneration were examined in 41 autopsy cases of Pick's disease. Based on the degree of SPN degeneration, these cases were arranged into four groups: 1) group I (severely degenerate; 19.5%), 2) group II (moderately degenerate; 22.0%), 3) group III (mildly degenerate; 36.5%), and 4) group IV (non-degenerate; 22.0%). 17 of the 41 cases had a definite (moderate to severe) SPN degeneration. The striatum, especially the caudate nucleus, was most frequently and most severely affected, while the internal segment of the globus pallidus was least frequently and least severely affected. In general, the oral portions of the SPN nuclei were more severely involved. In addition, in the putamen and globus pallidus the dorsomedial portions adjacent to the internal capsule were apt to be affected more markedly than the other portions. In the substantia nigra the degeneration tended to be more predominant in the pars reticulata than in the pars compacta, although both were usually involved. In addition, the medial to central portions of the substantia nigra were more vulnerable. In comparing the severely and moderately degenerate groups (groups I and II) with the mildly and non degenerate groups (groups III and IV), the former had more female cases, longer duration of illness, and more third-stage cases. In addition, the former contained more cases with lower brain weight and (predominant) frontal atrophy type, and more atypical cases without Pick bodies, or with symmetrical pyramidal tract degeneration or with combined traumatic lesions. It is notable that in all cases with definite SPN degeneration no extrapyramidal involuntary movements had been detected.     

Pick's disease: alpha- and beta-synuclein-immunoreactive Pick bodies in the dentate gyrus

Recent studies have shown that neurofibrillary tangles frequently coexist with alpha-synuclein (alpha-S)-positive fibrillary inclusions in the limbic system in Alzheimer's disease. To elucidate whether alpha-, beta- and gamma-S immunoreactivity is present in Pick bodies (PBs), we examined immunohistochemically and immunoelectron microscopically the brains from three patients with Pick's disease. Numerous PBs were distributed widely, and were occasionally immunoreactive for alpha-S and beta-S, but not for gamma-S in all three cases. However, these immunoreactive PBs were almost all restricted to the dentate gyrus. Despite the co-localization of phosphorylated tau and alpha-S or beta-S (as evidenced by double-labeling immunohistochemistry), immunoelectron microscopy revealed that alpha-S and beta-S immunoreactivity occurs in granular and vesicular structures, but not in filamentous structures. These findings suggest that alpha-S and beta-S are up-regulated in the neuronal perikarya but they are not incorporated into the constituent filaments of PBs, and that the preferential distribution of alpha-S- and beta-S-positive PBs in the dentate gyrus may represent the cellular response to PB formation in this particular system.     

Distribution of basal ganglia lesions in diffuse neurofibrillary tangles with calcification: a clinicopathological study of five autopsy cases

We investigated five Japanese autopsy cases of diffuse neurofibrillary tangles with calcification (DNTC), both clinically and pathologically, and examined the degree and distribution of the basal ganglia lesions, especially in the amygdala, striatum, pallidum, and substantia nigra. The lesions in the amygdala, striatum, and pallidum were classified into three categories (mild, moderate, and severe). The lesions in the substantia nigra were qualitatively judged, compared with normal controls. Severe dementia was observed in four cases neuropathologically showing pronounced neuronal loss in the cerebral cortex, but one case without neuronal loss in the cerebral cortex showed mild memory disturbance. Extrapyramidal signs were evident in three cases. Obvious neuronal loss in the substantia nigra with the presence of Lewy bodies was noticed in four cases. Basal ganglia lesions in all five cases were uniform: the amygdala showed severe to moderate lesions, the caudate nucleus moderate to slight lesions, and the putamen and pallidum slight lesions to normal. Furthermore, the lesions in the amygdala were more prominent in the basolateral group than in the corticomedial group, inconsistent with those in the amygdala of Alzheimer's disease. Moderate lesions were evident in the basolateral group of the amygdala in the case without neuronal loss in the cerebral cortex. In DNTC, the degree and distribution of the basal ganglia lesions, except for nigral lesions, were analogous to those found in Pick's disease with Pick bodies. These clinicopathological findings may contribute to the elucidation of the clinicopathological hallmarks in this disorder.     

Clustering of Pick bodies in the dentate gyrus in Pick's disease

In patients with Pick's disease (PD), high densities of tau positive Pick bodies (PB) have been observed within the granule cell layer of the dentate gyrus. This study investigated the spatial patterns of PB along the granule cell layer in coronal sections of the hippocampus in eight patients with PD. In all patients, there was evidence of clustering of PB within the granule cell layer; however, there was considerable variation in the pattern of clustering. In five patients, the clusters of PB were regularly distributed along the dentate gyrus, and in two of these patients, the smaller clusters were aggregated into larger superclusters. In three patients, a single large cluster of PB, more than 1200 μm in diameter, was present. Clustering of PB may reflect a primary degenerative process within the granule cells or the degeneration of pathways that project to the dentate gyrus.     

The spatial patterns of Pick bodies,Pick cells and Alzheimer's disease pathology in Pick's disease

The spatial patterns of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) were studied in the frontal and temporal lobe in nine cases of Pick's disease (PD). Pick bodies exhibited clustering in 41/44 (93%) of analyses and clusters of PB were regularly distributed parallel to the tissue boundary in 24/41 (58%) of analyses. Pick cells exhibited clustering with regular periodicity of clusters in 14/16 (88%) analyses, SP in three out of four (75%) analyses and NFT in 21/27 (78%) analyses. The largest clusters of PB were observed in the dentate gyrus and PC in the frontal cortex. In 10/17 (59%) brain areas studied, a positive or negative correlation was observed between the densities of PB and PC. The densities of PB and NFT were not significantly correlated in the majority of brain areas but a negative correlation was observed in seven of 29 (24%) brain areas. The data suggest that PB and PC in patients with PD exhibit essentially the same spatial patterns as SP and NFT in Alzheimer's disease (AD) and Lewy bodies (LB) in dementia with Lewy bodies (DLB). In addition, there was a spatial correlation between the clusters of PB and PC, suggesting a pathogenic relationship between the two lesions. However, in the majority of tissues examined there was no spatial correlation between the clusters of PB and NFT, suggesting that the two lesions develop in association with different populations of neurons.     

Basal ganglia lesions in corticobasal degeneration differ from those in Pick's disease and progressive supranuclear palsy: A topographic neuropathological study of six autopsy cases

The distribution of the lesions of the basal ganglia including the striatum, pallidum and subthalamic nucleus were investigated neuropathologically in six Japanese autopsy cases of corticobasal degeneration (CBD) using routine staining including the hematoxylin-eosin (HE) and Holzer methods. We compared the distribution of these lesions with those reported in Pick's disease and progressive supranuclear palsy (PSP). The lesions were classified as mild, moderate or severe. The extent and distribution of basal ganglia lesions in all six cases was uniform: the pallidum showed severe lesions, the striatum moderate lesions, and the subthalamic nucleus mild lesions. In CBD, the degree and distribution of the lesions within the basal ganglia differed from those reported for Pick's disease and PSP; in Pick's disease the lesions of the striatum are more prominent than that of the pallidum, and in PSP the involvement of the subthalamic nucleus is more pronounced than that of the striatum. These neuropathological findings have implications for the morphological differential diagnosis among Pick's disease, CBD, and PSP.     

Fine structure of the Pick and Hirano bodies in a case of Pick's disease

Summary Brain tissue from an autopsied case of Pick's disease was studied by light and electron microscopy. Intraneuronal argentophilic Pick bodies were most numerous in the pyramidal cells of the hippocampus. By electron microscopy, these inclusions consisted of a conglomeration of granules enmeshed in an irregular network of proliferated neurofilaments. There were also multiple eosinophilic juxtaneuronal structures (Hirano bodies). By electron microscopy these consisted of interwoven sheaves of beaded and continuous filaments. The possible location of the Hirano bodies within degenerating axonal terminals is discussed.

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Zusammenfassung Hirngewebe eines Falles von Pickscher Krankheit wurde licht-und elektronenmikroskopisch untersucht. Intraneuronale argentophile Picksche Körper wurden am zahlreichsten in den Pyramidenzellen des Hippocampus gefunden. Elektronenoptisch bestanden die Einschlußkörper aus einer Zusammenballung von körnigen Gebilden, die in einem unregelmäßigen Netz von vermehrten Neurofilamenten verstreut lagen. Viele eosinophile Hiranosche Körper fanden sich in nächster Nachbarschaft von Nervenzellen. Diese Körper bestanden aus verflochtenen Schichten von geperlten oder glatten Filamenten. Die mögliche Lokalisation der Hiranoschen Körper innerhalb von degenerierenden Axonendigungen wird diskutiert.

     

Alterations of muscarinic acetylcholine receptors in atypical Pick's disease without Pick bodies

BACKGROUND: Atypical Pick's disease without Pick bodies is a type of frontotemporal dementia characterised by semantic dementia and temporal dominant lobar atrophy with ubiquitinopathy. No neurochemical analyses have ever been reported in this condition. OBJECTIVE: To investigate muscarinic acetylcholine receptors (mAchR) and their subtypes (M1-M4) in atypical Pick's disease. SUBJECTS: Five cases of atypical Pick's disease were studied. They were compared with nine control cases, 11 cases of Alzheimer's disease, and seven cases of dementia with Lewy bodies. METHODS: A [(3)H]quinuclidinyl benzilate (QNB) binding assay and an immunoprecipitation assay using subtype specific antisera were used. RESULTS: The total amount of mAchR in the temporal cortex was lower in atypical Pick's disease than in controls or Alzheimer's disease cases, but there were no significant differences between the three groups in the frontal cortex. In the temporal cortex, there was a smaller proportion of M1 receptors in atypical Pick's disease than in the controls or in the patients with Alzheimer's disease and dementia with Lewy bodies. In contrast, the proportion of M2 receptor was higher in atypical Pick's disease than in the other three groups. CONCLUSIONS: Depletion of postsynaptic cholinoreceptive neurones in the temporal cortex is more severe in atypical Pick's disease than in other neurodegenerative dementing disorders.     

Morel's laminar sclerosis showing apraxia of speech: Distribution of cortical lesions in an autopsy case

A 57‐year old man with chronic alcoholism presented with apraxia of speech and disturbance of consciousness. He had a history of gastrectomy and had been drinking alcohol. The symptoms improved with administration of thiamine, but he later developed diarrhea and delirium, and died approximately 40 days after the onset. Autopsy findings were consistent with Wernicke's encephalopathy and pellagra encephalopathy. Furthermore, laminar cortical necrosis with vacuoles and astrocytosis was found in the second and third layers of the bilateral frontal cortices, suggesting Morel's laminar sclerosis. The lesions were mainly located in the bilateral primary motor cortices. Involvement of the lower part of the left primary motor cortex may be associated with apraxia of speech in our case.     

Coexistence of Pick bodies and atypical Lewy bodies in the locus ceruleus neurons of Pick's disease

We observed abundant Pick argentophilic inclusion bodies (PBs) as well as some atypical Lewy bodies (LBs) in the locus ceruleus (LC) from a patient with Pick's disease. In addition, there were a few neurons which contained both PBs and LBs. PBs in the LC frequently appeared multiple and had lobulated or irregular shapes, though their ultrastructural elements were the same as those of the PBs appearing in the cerebral cortex, and consisted of randomly arranged smooth-surfaced straight tubules of 15 nm in diameter, mixed with a small number of long-period constricted fibrils. The ultrastructure of the LB coexisting with PB was identical with that previously reported; a dense core was surrounded by concentric layers of radially oriented 10-nm filaments and was clearly distinguishable from the PB. Immunohistochemical examination with various antibodies related to neurofibrillar pathology demonstrated that anti-tau antibodies reacted positively with both PB and the rim portion of LB in the present case; an unusual finding for LB. The anti-neurofilament 200-kDa protein stained only LBs, even when PBs and LBs coexisted in the same neuron. These findings show that two kinds of neuronal fibrillar inclusions, whose underlying cytoskeletal abnormalities are thought to be different, can coexist in the same neuron. In addition, the formation of multiple, lobulated PBs may suggest some particularity of cytoskeletal composition of the LC neurons.     

Laminar distribution of Pick bodies, Pick cells and Alzheimer disease pathology in the frontal and temporal cortex in Pick's disease

Lesions in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have distinct laminar distributions in the cortex. The objective of the present study was to test the hypothesis that the lesions characteristic of Pick's disease (PD) and AD have distinctly different laminar distributions in cases of PD. Hence, the laminar distribution of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) was studied in the frontal and temporal cortex in nine patients with PD. In 57% of analyses of individual cortical areas, the density of PB was maximal in the upper cortex while in 25% of analyses, the distribution of PB was bimodal with density peaks in the upper and lower cortex. The density of PC was maximal in the lower cortex in 77% of analyses while a bimodal distribution was present in 5% of analyses. The density of NFT was maximal in the upper cortex in 50% of analyses, in the lower cortex in 15% of analyses, with a bimodal distribution in 4% of analyses. The density of SP did not vary significantly with cortical depth in 86% of analyses. The vertical densities of PB and PC were negatively correlated in 12/21 (57%) of brain areas. The maximum density of PB in the upper cortex was positively correlated with the maximum density of PC in the lower cortex. In 17/25 (68%) of brain areas, there was no significant correlation between the vertical densities of PB and NFT. The data suggest that the pathogenesis of PB may be related to that of the PC. In addition, although in many areas PB and NFT occur predominantly in the upper cortex, the two lesions appeared to affect different neuronal populations.     

Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases

We describe three cases of early- (cases 1–3, 28–39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinhibition, and impulsiveness. Spastic paraparesis was observed in only one early-onset case. Hematoxylin-eosin-stained sections showed numerous CWPs, especially in the temporal cortex, in all cases. Bielschowsky-stained sections showed neurofibrillary tangles and minor neuritic changes surrounding the CWPs in three cases, but not in case 2. Gallyas-Braak-stained sections showed weak argyrophilia in homogeneous material of the CWPs in cases 2 and 4. Quantitative analysis demonstrated that A42 was deposited more predominantly than A40 in three cases. However, in case 2, approximately twice as much A40 as A42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. -Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-A component of AD amyloid (NAC), a central fragment of -synuclein, were found in case 3. In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of A40 and A42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) A deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving -synuclein and NAC deposition.