beta-Amyloid deposits within the cerebellum of persons older than 80 years of age.

The cerebellum, frontal cortex, hippocampal and parahippocampal regions of 100 patients older than 80 years, most of whom had died of stroke, were examined. Eighteen percent were diagnosed as clinically demented. On the specimens labeled previously with Thioflavin S and Bielschowsky method, immunohistochemical studies were performed with Fab (antigen-binding fragment) of the anti beta-amyloid antibody 4G8. Positive amyloid immunoreactivity was observed in the cerebrum in 71 of 100 cases, Cerebella of 31 subjects of 71 with cerebral amyloidosis also revealed amyloid deposits. They appeared in various morphological forms, such as diffuse plaques and focal subpial deposits, as well as classical and primitive neuritic plaques. Cases with amyloid in the cerebellum alone were not observed. Beta-amyloid deposits in the cerebellum were associated with a significant number of beta-amyloid plaques in the cerebrum, which showed other Alzheimer-type pathology, also in individuals without clinical symptoms of dementia. There was no correlation either between cerebellar amyloid deposits and clinical cerebellar symptoms or between the presence of diabetes mellitus, arterial hypertension, and neuropathological changes. A clear association of microglial cells with amyloid deposits in the cerebellum was demonstrated. In our experience, LN-1 and RCA-1 were not as suitable for formalin-fixed paraffin-embedded tissue, as was anti-ferritin. Negative staining for tau-1 and positive staining for anti-ubiquitin characterized neurites within primitive and classical plaques. No neurofibrillary pathology was detected in the cytoplasm of cerebellar neurons when we used anti tau-1 labeling.     

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease

Summary Immunocytochemical staining with monoclonal antibodies to the -protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the -protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word plaques does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto-and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.Supported in part by grants 5-AGO-4220-05 and 5-HD-22634-02 from the National Institutes of Heath     

The −22c/t polymorphism in presenilin 1 gene is not connected with late-onset and early-onset familial Alzheimer’s disease in Poland

Summary. The –22c/t polymorphism in the promoter of the presenilin 1 gene is associated with increased risk for Alzheimers disease (AD) in some populations. It was shown that –22c allele is connected with two-fold decrease in promoter activity. We studied the impact of the polymorphism in groups of Polish late-onset and early-onset AD patients. Our results suggest that –22c/t polymorphism is not connected with AD in Polish population. The –22t allele showed a high degree of linkage disequilibrium with –2797 insertion of 13bp. An additional –2923g/t polymorphism is also not connected with –22c/t and is not a risk factor for AD.     

Interaction evaluation between APOE epsilon 4 alleles and hippocampal atrophy. Preliminary communication

In CT images the atrophy of medial parts of temporal lobes was evaluated in 60 patients with Alzheimer-type dementia. In the genotype of 30 patients at least one APOE epsilon 4 allele was identified, the other 30 patients served as the control group. The results of in vivo measurements of temporal lobe atrophy in the examined patients did not show statistically significant relations with APOE genotype which was probably due to entirely different nature and application of both tests.     

Frequency and intensity of behavioral and psychological symptoms in the course of Alzheimer's disease

The aim of the study was: 1) to estimate the occurrence and intensity of some psychopathological symptoms in the course of Alzheimer's disease, and 2) to examine whether the occurrence of behavioral and psychological symptoms increases with the deepening of dementia process among persons with Alzheimer's disease living in their homes with outpatient treatment. The study was conducted among 94 persons (38 men and 56 women ageing from 52 to 86 years (x = 72.4 +/- 6.9), with education: from 2 to 17 years (x = 11.2 +/- 3.7). Three subgroups were selected for study with regard to the intensity of dementia process, estimated according to Clinical Dementia Rating (CDR): very mild (n = 16, x = 71.4 +/- 6.7), mild (n = 43, x = 72.6 +/- 7.9), moderate (n = 35, x = 72.5 +/- 6.9). Subjects in group II and III fulfill diagnostic criteria of dementia according to ICD-10, DSM IV and criteria of probable AD according to NINCDS-ADRDA. In the estimation of occurrence of behavioral and psychological disturbances: Alzheimer's Disease Assessment Scale--non-cognitive behavior (ADAS-non-cog) and subscale "Change in Personality, Interests, Drive" of Blessed Dementia Scale were used. The results have shown that with the progress of dementia process, the occurrence of the following psychopathological symptoms such as: hallucinations, intensive motor activity, purposeless hyperactivity, pacing, rigidity increases and there is a relinquishment of hobbies. In addition, regardless of the stage of dementia, such behaviors as: apathy, depression, tearfullness, impaired emotional control and disturbances of appetite were observed relatively frequently.     

Cerebellar granular layer degeneration in small cell lung cancer: paraneoplastic cerebellopathy or artifact?

The aim of our study was to ascertain whether granular cell degeneration represents uniquely an artifactual or a supravital event in patients with oat cell carcinoma. The material includes 52 cases of small cell lung cancer (SCLC). Formalin fixed and paraffin embedded representative cerebellar slides were stained routinely (HE, Klüver-Barrera), and some of them served as material for immunohistochemical study. The following antibodies were used: anti-ferritin, anti-GFAP, anti-IgG and anti-C3 complement fraction. Finally 5 cases out of our material could be diagnosed as paraneoplastic cerebellar degeneration (PCD), on the basis of lack of metastases within the CNS and concomitant intensive loss of Purkinje and granule cells. Clinically the cerebellar syndrome was disclosed in 3 cases. In the granular layer prevalence of microglial cell reaction was noted. GFAP-labeled astroglia were not demonstrated in the same intensity. Antisera to the C3 complement fraction showed moderate staining of Purkinje cell cytoplasm and in some cases also of granule cells. IgG immunostaining was disclosed in Purkinje cell cytoplasm and in 4 cases also in granule cell nuclei. The immunopathological changes presently observed and glial cell proliferation could be evidence for a nonartifactual origin of PCD.     

Cell cycle regulation distinguishes lymphocytes from sporadic and familial Alzheimer's disease patients

Cell cycle (CC) reactivation in neurons seems to underlie the development of Alzheimer's disease (AD). We analyzed whether CC alterations can be detected in immortalized lymphocytes from patients with the sporadic and the familial form of AD (SAD and FAD). Real-time polymerase chain reaction (PCR)-arrays, immunoblotting, and flow cytometry demonstrated differences in the regulation of G1/S phases between SAD lymphocytes and cells from nondemented subjects, as well as between SAD and FAD cells. SAD compared to FAD lymphocytes showed differences in expression profiles of the 90 CC genes, and a marked increase in the level of the p21 protein, which promotes G1-arrest. Accordingly, SAD but not FAD cells had a prolonged G1-phase. γ-secretase inhibition did not change the CC profiles of the cell lines. These data show that SAD involves a prolongation of the G1 phase driven by p21 pathway, which is not activated in FAD cells. Thus, the mechanism in SAD differs from FAD. Moreover, disturbances of the CC in lymphocytes have a potential diagnostic value.     

Mitochondrial haplogroup H and Alzheimer's disease--is there a connection?

We evaluated the involvement of the major Caucasian-specific mitochondrial haplogroups (H, I, J, K, T, U, V, W and X), haplogroup clusters (HV, UK, TJ, IWX) and two functional mtSNPs (4216, 4917) in the pathogenesis of Alzheimer's disease (AD) in the Polish population. The frequency distribution of mtDNA haplogroups was non-randomly associated with APOE4 status (chi(2)=73.17, df=1, p<0.0001, OR=5.97, 95% CI 3.90-9.12), however, no haplogroup-specific neutralizing of the APOE4 allele influence was detected. Multivariate analysis suggested the opposite-APOE4 status could modulate the effect of mtDNA haplogroups. We found that HV cluster is significantly associated with the risk of AD, regardless of the APOE4 status (OR=1.59, 95% CI, 1.04-2.44, p=0.032). Contrary to the previous studies, we report no evidence for the involvement of haplogroup U, K, J or T in AD risk. We conclude that further analysis of subtypes of haplogroup H would be necessary to decipher the relation of HV cluster with AD.