Biomedical subjects

N Bogdanovic

Publications and source records attributed to N Bogdanovic.

At least 37 records · Page 2Linked to original sources

PubMed2000

No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.

A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.

Aged↗

PubMed2000

Reduction of the synaptic protein rab3a in the thalamus and connecting brain regions in post-mortem schizophrenic brains.

Although the psychotic symptoms in schizophrenia can be alleviated by treatment with dopaminergic receptor antagonists, the etiology and underlying neurochemical pathology remains obscure. Both neuropathological and magnetic resonance imaging studies have found evidence for neuronal loss and atrophy in the thalamus in schizophrenia, implicating this key structure for gating information to cortical areas in the pathophysiology. Recent studies have also found evidence of synaptic loss in the thalamus in schizophrenia. To further examine possible synaptic disturbances, we studied the synaptic related protein rab3a as a marker for synaptic density, using both quantitative Western blotting and immunohistochemistry. The material consisted of brains from 22 schizophrenic patients (mean age 79.3 years), and 24 control subjects (74.8 years). Reduced rab3a protein levels were found in the left thalamus in schizophrenia (0.47 +/- 0.17 vs. 1.00 +/- 0.18; p < 0.0001), while a less marked decrease was found also in the right thalamus (0.75 +/- 0.13 vs. 1.00 +/- 0.09; p < 0.0001). Immunohistochemistry, performed on two schizophrenic and two control brains, revealed that rab3a immunoreactivity was most reduced in the left anterior and mediodorsal thalamic nuclei. Therefore, we extended the study to brain regions connected these thalamic nuclei. Reduced rab3a protein levels were found schizophrenia also in the frontal cortex, hippocampus, gyrus cinguli, and parietal cortex, while no significant differences were found in the temporal cortex, or in cerebellum. The reduction in rab3a was not found to be secondary to confounding factors such as age-differences, post-mortem delay time, generalized brain atrophy, or antipsychotic medication. Therefore, the reduction of rab3a probably reflects synaptic disturbances, possibly synaptic loss, in the limbic system and neocortical areas, in schizophrenia. This part of the brain is known to be involved in behavioral and emotional control, and thus to be crucial for higher mental functions, suggesting that synaptic disturbances in the limbic system may be of importance in the development of psychotic symptoms in schizophrenia.

Adult↗

PubMed2000

Growth-associated protein GAP-43 in the frontal cortex and in the hippocampus in Alzheimer's disease: an immunohistochemical and quantitative study.

We studied the growth-associated protein, GAP-43 (also called neuromodulin and B-50) in post-mortem brain tissue using immunohistochemistry and quantitative Western blotting, from patients with Alzheimer's disease (AD) and age-matched control subjects. By immunohistochemistry, we found a clear reduction of GAP-43 in the frontal cortex, while in the hippocampus, there was a marked reduction in some areas (dentate molecular layer, stratum moleculare and radiale of CA1 and CA4), while not in other areas (stratum lacunosum, pyramidale and oriens of CA1). Moreover, in the hippocampus, neuritic staining was prominent, and was often associated with senile plaques. Quantitative analysis showed that GAP-43 was significantly reduced in AD, both in the frontal cortex (70% of the control value, p < 0.01) and in the hippocampus (81% of the control value, p < 0.05). In the frontal cortex, there was a significant negative correlation between GAP-43 and duration of dementia (r = -0.58; p < 0.02) and a positive correlation between GAP-43 and the synaptic vesicle-specific protein rab3a (r = 0.62; p < 0.05), while no such correlation were found in the hippocampus. In contrast, a significant positive correlation was found between GAP-43 and the number of senile plaques in the hippocampus (r = 0.64; p < 0.05), but not in the frontal cortex. GAP-43 is known to be involved in maintenance of synapses and in neuritic regeneration. Our findings may suggest that in the frontal cortex, GAP-43 levels decline as a consequence of the synaptic degeneration, while in the hippocampus, sprouting processes, involving GAP-43, are active.

Aged↗

PubMed2000

Density profiles of Alzheimer disease regional brain pathology for the huddinge brain bank: pattern recognition emulates and expands upon Braak staging.

Density profiles of Alzheimer's disease (AD) regional brain pathology were constructed for 249 subjects in the Huddinge Brain Bank. Counts per square millimeter for neurofibrillary tangles (NFT), diffuse plaques (DP), and neuritic plaques (NP) in 38 areas were investigated using a pattern recognition technique called GoM. The seven distributional profiles of AD neuropathology emulated and expanded upon Braak staging illustrating induction (Groups 1-3) and clinical progression (Groups 4-7). Normal aging represented limited AD changes, few NFT in the entorhinal cortex and hippocampal CA1 (Group 1). The threshold for possible AD was NFT in the subiculum (Group 2), found with DP in the neocortex. Temporal medial NFT was the threshold for probable AD (Group 4). The 'oldest-old', often demented without brain atrophy, had extensive entorhinal/CA1 NFT and cortical DP, but few cortical NFT or NP (Group 5). A second subtype 'disconnection' (Group 6) lacked AD pathology for a specific set of subcortical and cortical areas. Accumulation of NFT in first-affected areas continued through end-stage disease (Group 7), with apparent rapid transition of DP to NP in the cortex during clinical progression. The evolution of AD is a highly ordered sequential process. Pattern recognition approaches such as GoM may be useful in better defining the process.

Alzheimer Disease↗

PubMed1999

Quantitative autoradiography of [3H]forskolin binding sites in post-mortem brain staged for Alzheimer's disease neurofibrillary changes and amyloid deposits.

Adenylyl cyclase (AC) signal transduction has been shown to be affected in Alzheimer's disease (AD). Deficits have been described in different components of the system, from the receptor to the effector level. [3H]forskolin is a diterpene that binds with high affinity to AC. In the present report, we used autoradiography to study [3H]forskolin binding to sections of entorhinal cortex and hippocampus from 23 cases staged for AD pathology according to Braak and Braak [Acta Neuropathol. 82 (1991) 239-259]. This protocol defines six stages according to neurofibrillary changes, which start in the entorhinal region (stages I-II), spread to the hippocampus (stages III-IV) and finally to the isocortical areas (stages V-VI). The amyloid classification includes three stages in which the basal isocortex is first affected (stage A), followed by other isocortical association areas (stage B) and finally the primary isocortical areas (stage C). We also studied the effects of the GTP-analogue Gpp[NH]p on binding, in order to detect changes in G-protein-AC coupling. We used two different concentrations of Gpp[NH]p, that were previously reported to inhibit and stimulate [3H]forskolin binding via Gi and Gs, respectively. Results showed that [3H]forskolin binding declined significantly with staging for neurofibrillary changes only in the entorhinal region (P < 0.05, ANOVA). In addition, the decrease in [3H]forskolin binding observed in the presence of 1 microM Gpp[NH]p diminished significantly with staging in the entorhinal region (P < 0.05, ANOVA). No significant changes were seen with amyloid staging, with the exception of the CA1 subfield of the hippocampus, where [3H]forskolin binding in the absence of Gpp[NH]p was significantly decreased at stage B compared with all other stages (P < 0.05, ANOVA). In conclusion, our results showed a very limited decrease in [3H]forskolin binding with the progression of AD pathology, suggesting that the AC levels may be largely preserved in the disease. The specific change in the effect of a low concentration of Gpp[NH]p on the binding could indicate the loss of Ca2+/calmodulin-sensitive AC isoforms in AD.

Adenylyl Cyclases↗

PubMed1999

Ultrastructural analysis of the hippocampus of adult rats after long-term adrenalectomy.

Removal of adrenal steroids modulates various functions in the brain. However, adrenalectomy (ADX) induced cell death in the hippocampal formation of the adult rat is a recently described phenomenon. We undertook this ultrastructural study on long-term adrenalectomized (5 months) rats to investigate the mode of cell death in the hippocampus. Our results showed apoptotic changes in the hippocampus. In addition we have observed other types of degeneration in the hippocampal neurons. The novel finding in this study is that different morphological patterns of cell death were evident both in the dentate gyrus and in the pyramidal areas, which may reflect different stages of the same death process.

Adrenalectomy↗

PubMed1999

The synaptic-vesicle-specific proteins rab3a and synaptophysin are reduced in thalamus and related cortical brain regions in schizophrenic brains.

Two synaptic-vesicle proteins, rab3a and synaptophysin, have been studied on post-mortem brain tissues of schizophrenics and healthy controls. We found significantly reduced levels of rab3a in thalamus (p<0.001); for both proteins in gyrus cinguli and hippocampus (p<0.0001); for rab3a in frontal and parietal cortex (p<0.05); and no differences in temporal cortex or cerebellum in schizophrenics compared with controls. Reduced synaptic density may be a prominent feature of the molecular neuropathology of schizophrenia.

Adult↗

PubMed1999

A quantitative autoradiographic study of [3H]cAMP binding to cytosolic and particulate protein kinase A in post-mortem brain staged for Alzheimer's disease neurofibrillary changes and amyloid deposits.

The cAMP-dependent protein kinase (PKA) has been implicated in the Alzheimer's disease pathology of abnormal tau phosphorylation leading to neurofibrillary tangle (NFT) formation, as well as in amyloid precursor protein alpha-secretase processing. In the present study, we determined whether [3H]cAMP binding to cytosolic and particulate PKA showed any relationship to the extent of Alzheimer's disease pathology at post-mortem. Autoradiographic [3H]cAMP binding to cytosolic and particulate PKA was measured in sections of entorhinal cortex/hippocampal formation from 23 cases that had been staged for Alzheimer's disease-related neurofibrillary changes and amyloid deposits according to Braak and Braak [H. Braak, E. Braak, Neuropathological staging of Alzheimer's-related changes, Acta Neuropathol. 82 (1991) 239-259]. [3H]cAMP binding to cytosolic PKA showed statistically significant reductions in the entorhinal cortex (P<0.01, ANOVA) with respect to neurofibrillary changes. Post-hoc analysis with Fisher's PLSD test showed significant reductions of [3H]cAMP binding to cytosolic PKA at the isocortical stages (V and VI), compared to the non-pathological (O) (by 55%, P<0.01), transentorhinal (I and II) (by 58%, P<0.001) and limbic (III and IV) (by 45%, P<0.05) stages. A significant reduction (by 25%, P<0.05) was also seen in the transentorhinal compared to the limbic stages. [3H]cAMP binding to cytosolic PKA showed no significant alterations with respect to neurofibrillary changes in either the subiculum, CA1-CA4 subfields of the hippocampus or the dentate gyrus. [3H]cAMP binding to cytosolic PKA also showed significant declines in the entorhinal cortex (P<0.01) and subiculum (P<0.05) with respect to staging for amyloid deposits. Post-hoc analysis with Fisher's PLSD test showed significant reductions of [3H]cAMP binding to cytosolic PKA in the entorhinal cortex at amyloid stage C compared to stages O (by 41%, P<0.01) and A (by 38%, P<0.01). In the subiculum, there were significant reductions of [3H]cAMP binding at stages C (by 41%, P<0.01) and B (by 40%, P<0.05), respectively, compared to stage O. [3H]cAMP binding to particulate PKA did not show significant relationships to staging for either neurofibrillary changes or amyloid deposits in either the entorhinal cortex or any of the hippocampal subregions. These findings suggest that whereas [3H]cAMP binding to cytosolic PKA in the entorhinal cortex is reduced with progression of neurofibrillary and amyloid pathology, other hippocampal regions show a preservation of cytosolic and particulate PKA even in late stage pathologies.

Aging↗

PubMed1999

Sound stimulation increases calcium-binding protein immunoreactivity in the inferior colliculus in mice.

The numerical density of calbindin D-28k and parvalbumin immunopositive neurons in the inferior colliculus (IC) in mice was increased after sound stimulation. An increased number of calbindin positive neurons was found in the deep layers of the external cortex (EC) and particularly in the dorsal cortex (DC) and commissural nucleus (NCO). An increase of parvalbumin positive neurons was found in the EC, central nucleus (ICC) and DC, but not in the NCO. The increased immunoreactivity related to sound exposure suggests the appearance of neurons which express these proteins after sound stimulation. The up-regulation of calcium-binding proteins in these neurons may be due to their protective role against overstimulation, their response to a higher auditory metabolic activity, or increasing effect of excitatory inputs after noise-induced hearing loss.

Acoustic Stimulation↗

PubMed1999

GABA transporters (GAT-1) in Alzheimer's disease.

The presynaptically located gamma-aminobutyric acid (GABA) transporter (GAT-1) was studied in a group of patients with Alzheimer's disease (AD) and in a control group using the GAT-1 selective radioligand [3H]tiagabine. Post mortem brain tissue from frontal cortex, temporal cortex, and caudate nucleus from 18 AD patients and 23 age-matched controls were studied. The binding was saturable (Kd 26 nM) and region specific. There were no significant differences between the groups with respect to the binding capacity (Bmax) and binding affinity (Kd). The unaltered [3H]tiagabine binding to GAT-1 protein indicates that intrinsic GABA neurons are spared in Alzheimer's disease.

Aged↗

PubMed1999

Neuronal nicotinic receptor deficits in Alzheimer patients with the Swedish amyloid precursor protein 670/671 mutation.

The influence of beta-amyloid on cholinergic neurotransmission was studied by measuring alterations in nicotinic acetylcholine receptors (nAChRs) in autopsy brain tissue from subjects carrying the Swedish amyloid precursor protein (APP) 670/671 mutation. Significant reductions in numbers of nAChRs were observed in various cortical regions of the Swedish 670/671 APP mutation family subjects (-73 to -87%) as well as in sporadic Alzheimer's disease (AD) cases (-37 to -57%) using the nicotinic agonists [3H]epibatidine and [3H]nicotine, which bind with high affinity to both alpha3 and alpha4 and to alpha4 nAChR subtypes, respectively. Saturation binding studies with [3H]epibatidine revealed two binding sites in the parietal cortex of AD subjects and controls. A significant decrease in Bmax (-82%) for the high-affinity site was observed in APP 670/671 subjects with no change in K(D) compared with controls (0.018 nM APP 670/671; 0.036 nM control). The highest load of neuronal plaques (NPs) was observed in the parietal cortex of APP 670/671 brains, whereas the number of [3H]nicotine binding sites was less impaired compared with other cortical brain regions. Except for a positive significant correlation between the number of [3H]nicotine binding sites and number of NPs in the parietal cortex, no strict correlation was observed between nAChR deficits and the presence of NPs and neurofibrillary tangles, suggesting that these different processes may be closely related but not strictly dependent on each other.

Aged↗

PubMed1998

Alzheimer changes are common in aged drivers killed in single car crashes and at intersections.

With increasing age, diseases affecting the cognitive functions are more frequent. These diseases may increase the risk for fatal car crashes. We analyzed the frequency of neuropathological alterations characteristic of Alzheimer's disease (i.e. neuritic and diffuse plaques, and neurofibrillary tangles) in two association areas of the brain, parietal and frontal cerebral cortex, from 98 fatally injured aged drivers. In the age groups of 65-75 and over 75 years of age, 50% and 72% of the drivers, respectively, had neuritic plaques in either parietal and/or frontal cortex. In 14% of all killed drivers the number of neuritic plaques reached the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) age-related histologic score C, which indicates the diagnosis of Alzheimer's disease (AD), and an additional 33% had score B, which suggests the diagnosis of AD. Neuropathological AD changes were most common in the brains of drivers killed in single vehicle crashes, followed by multivehicle crashes at intersections and least common in multivehicle crashes elsewhere, but the differences did not reach statistical significance. In a great majority (80-85%) of cases the killed aged driver was the guilty party of the crash. The results imply, that incipient AD may contribute to fatal crashes of aged drivers, and therefore the forensic autopsy of these victims should include neuropathological examination.

Accidents, Traffic↗

PubMed1998

Regional distribution of subtypes of nicotinic receptors in human brain and effect of aging studied by (+/-)-[3H]epibatidine.

Epibatidine, a potent nicotinic agonist, was used to study the regional distribution of nicotinic acetylcholine receptor binding sites in the human brain. Saturation studies performed in the human temporal cortex with (+/-)-[3H]epibatidine revealed binding to two binding sites with Kd and Bmax values of 0.018 and 4.2 nM, 12.7 and 15.4 fmol/mg protein, respectively. Competition studies with (+/-)-[3H]epibatidine/unlabelled nicotine or [3H]nicotine/unlabelled (+/-)-epibatidine showed binding to two binding sites in the human temporal cortex (Ki=0.16 and 12.6 nM; 0.007 and 0.3 nM, respectively). Similarly, when unlabelled nicotine was used to displace (+/-)-[3H]epibatidine, two binding sites were also revealed in the thalamus and the cerebellum of human brain (Ki=0.065 and 7.7 nM; 0.07 and 12.5 nM, respectively). The regional binding of (+/-)-[3H]epibatidine binding in human brain was somewhat different from that of [3H]nicotine. A proportionally higher binding was observed for (+/-)-[3H]epibatidine in the cerebellum and the thalamus compared to [3H]nicotine, probably reflecting different selectivity to nicotinic receptor subtypes. A marked significant age-related decrease in (+/-)-[3H]epibatidine binding was observed in the frontal and the temporal cortices (-79%, -84%, respectively) of human subjects between 56-85 years of age, which was similar to that of [3H]nicotine (-82%, -79%, respectively). The (+/-)-[3H]epibatidine binding in the cerebellum decreased significantly with age (-77%), while [3H]nicotine binding showed no significant age-related changes in this brain region. The findings indicate that a specifically modulate regional nicotinic receptors in human brain.

Aged↗

PubMed1998

Modulating calbindin and parvalbumin immunoreactivity in the cochlear nucleus by moderate noise exposure in mice. . A quantitative study on the dorsal and posteroventral cochlear nucleus.

The number of calbindin D-28k and parvalbumin immunoreactive (IR) neurons were characterized on sections from the cochlear nucleus, dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) using two-dimensional quantification. After noise exposure (6-12 kHz, 2 h, at either 80 dB SPL or 103 dB SPL), the number of calbindin and parvalbumin immunoreactive neurons increased in CBA/CBA mice. Quantitative analysis of calbindin-IR in the PVCN did not show a statistically significant difference between any of the groups, whereas statistically significant differences in calbindin-IR were found in the DCN for the 103 dB and 80 dB group compared to the control group, and 103 dB compared to the 80 dB group, respectively. A statistically significant increase in the number of parvalbumin-IR neurons in the PVCN and the DCN was evident in the 103 dB and 80 dB group compared to the control group, and in the 103 dB compared to the 80 dB group. The data indicate that increasing sound stimulation causes a graded increase in the expression of calcium-binding protein immunoreactivity in the DCN and PVCN neurons and neuropil. This increase of protein expression is due to increased positive immunoreactivity in 'silent' neurons. These findings implicate that these neurons have the possibility to react against trauma and display calbindin or parvalbumin as a rescue event. The ability to map sound-induced calcium-binding protein changes in auditory neurons may be useful in future studies designed for detecting early patterns of neurodegeneration and neuroprotection in the central auditory pathway.

Acoustic Stimulation↗

PubMed1998

Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration.

Cyclin-dependent kinase 5 (cdk5) is one of the candidate kinases involved in the abnormal hyperphosphorylation of tau. To have a direct effect on tau hyperphosphorylation, cdk5 protein levels and enzyme activity should be upregulated in especially those neurons that develop neurofibrillary tangles (NFTs). We studied the distribution of cdk5 immunoreactivity in neurons with or without early- and late-stage NFTs in hippocampal, entorhinal, transentorhinal, temporal and frontal cortices, and cerebellum of Alzheimer's disease (AD) and control brain. The immunocytochemical localisation of cdk5 was compared with that obtained using antibodies to PHF-tau (tau in paired helical filaments of NFTs, mAb AT8) and ubiquitin as markers of early and late stage NFTs, respectively. Immunoreactivities of cdk5 and PHF-tau were found in neuronal perikarya and processes of hippocampal, entorhinal, transentorhinal, temporal and frontal, and cerebellar cortices. An apparent increase of cdk5 immunoreactivity was seen in pretangle neurons and in neurons bearing early stage NFTs. These findings suggest that this kinase might be involved in the formation of NFTs at a relatively early stage in the neocortex.

Aged↗

PubMed1998

Changes in IGF-1 receptors in the hippocampus of adult rats after long-term adrenalectomy: receptor autoradiography and in situ hybridization histochemistry.

Alteration of insulin-like growth factor-1 (IGF-1) receptor and its mRNA after long-term adrenalectomy (ADX) was studied in the hippocampus by in vitro receptor autoradiography and in situ hybridization histochemistry, respectively. Significantly, decreased levels of IGF-1 receptor and its mRNA was noted in the dentate and CA1-CA4 regions of the hippocampus of the ADX animals, suggesting that the level and expression of IGF-1 receptors in the hippocampus is influenced by adrenal hormones.

Adrenal Cortex Hormones↗

PubMed1998

Loss of inositol 1,4,5-trisphosphate receptor sites and decreased PKC levels correlate with staging of Alzheimer's disease neurofibrillary pathology.

Inositol 1,4,5-trisphosphate (IP3), inositol 1,3,4,5-tetrakisphosphate (IP4) and protein kinase C (PKC) play important roles in the phosphoinositide hydrolysis signal transducing pathway. Several studies have shown severe deficits in both IP3 receptor levels and PKC levels and activity in Alzheimer's disease brain, although the relationship of these changes to disease pathology is poorly understood. In the present study, we determined the autoradiographic localization of [3H]IP3 and [3H]IP4 binding to their calcium mobilizing receptor sites and [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding to PKC in sections of entorhinal cortex/hippocampal formation and cerebellum from 24 cases that had been staged for Alzheimer's disease-related neurofibrillary changes and amyloid deposition according to Braak and Braak [Acta Neuropathol. Berl., 82 (1991) 239-259]. Results indicated that [3H]IP3 binding showed a trend towards a decline with staging for neurofibrillary changes in the entorhinal region (0.05 < P < 0.10, ANOVA) and subiculum (0.05 < P < 0.10). In the former region, [3H]IP3 binding showed a significant decline with staging for amyloid deposition (P < 0.05). [3H]IP3 binding in the CA1 region showed statistically significant declines with respect to both neurofibrillary changes and amyloid staging (P < 0.05). [3H]IP3 binding levels in the other hippocampal subregions were too low to quantify accurately. The binding of [3H]IP4 showed no significant changes with either neurofibrillary changes or amyloid staging in any of the regions investigated. In contrast, [3H]PDBu binding showed significant declines with neurofibrillary staging in the entorhinal region (P < 0.01), subiculum (P < 0.001), CA1 (P < 0.001), CA2 (P < 0.001), CA3 (P < 0.001) and CA4 (P < 0.0001) regions and the dentate gyrus (P < 0.0001). Of these regions, only the subiculum showed a significant decline of [3H]PDBu binding with amyloid staging. There were no significant neurofibrillary or amyloid stage-related changes in either [3H]IP3, [3H]IP4 or [3H]PDBu binding in the molecular layer of the cerebellum. These findings suggest that reduced IP3 receptor and PKC levels in the entorhinal cortex/hippocampal formation reflect and may be important for the progression of Alzheimer's disease neurofibrillary pathology. The data also suggests that hippocampal IP3 receptor loss is related to the extent of amyloid deposition.

Adult↗

PubMed1998

Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer's disease.

We studied the multifunctional protein clusterin (apolipoprotein J, SGP-2, SP-40,40) in brain tissue using quantitative Western blotting and immunohistochemistry. The material included postmortem brains from 19 patients with Alzheimer's disease (AD), 6 with vascular dementia (VAD), and 7 age-matched control subjects. Intense clusterin staining was found in the soma of both neuronal and astroglial cells. In addition, positive staining was found in a portion of senile plaques (SP) in AD brains. Quantitative analysis showed that clusterin levels were significantly increased in AD, both in frontal cortex (150% of the control value, P = 0.002) and in the hippocampus (179% of the control value, P < 0.001), while normal clusterin levels were found in cerebellum (104% of the control value). No significant changes were found in VAD. Within the AD group, there was a significant negative correlation between clusterin levels in hippocampus and severity of dementia (r = -0.40), while no such correlation was found in frontal cortex (r = 0.12). No significant correlations were found between clusterin levels and the number of SP or neurofibrillary tangles. No significant differences in clusterin levels were found in any brain region between AD patients possessing different numbers of the ApoE4 allele. The increased clusterin levels in AD brain, together with the absence of a correlation between SP counts and clusterin levels, and the finding that clusterin is only found in a smaller portion of SP do not suggest a link between clusterin and beta-amyloid dependence. Instead we hypothesize that the increase is part of a regional response in AD brain.

Aged↗