Bjertness, Espen; Torvik, Ansgar; lnce, Paul G.; Edwardson, James A. Author Information

Summary:Several studies have reported that the bulk aluminum (Al) concentration is increased in the brain in Alzheimer disease (AD), while other studies have failed to demonstrate an increase. Most of these investigations have had one or more methodological deficiencies, including lack of adequate neuropathological assessment; failure to age-match the control samples; small sample sizes, lacking statistical power; and geographical heterogeneity in the AD and control populations. The present population-based study of 92 clinically and histopathologically diagnosed AD patients and normal elderly nursing home residents was designed to avoid these potential biases. When a subsample of AD cases with the most severe brain pathology was compared with controls having no or minimal pathology, no statistically significant differences were found in the bulk aluminum concentration measured by graphite furnace atomic absorption spectrometry in frontal cortex (1.8 ± 0.7 vs. 1.7 ± 0.7 μg/g dry wt), temporal cortex (1.4 ± 0.3 vs. 1.5 ± 0.5 μg/g dry wt), liver (2.0 ± 1.3 vs. 2.0 ± 1.2 μg/g dry wt), or head of femur (2.4 ± 1.6 vs. 2.2 ± 1.0 μg/g ash wt). Within the whole series of 92 cases, there was no difference in the bulk aluminum concentration of the frontal cortex between individuals diagnosed as definite, probable, and possible cases of AD using the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. The density of senile plaques and neurofibrillary tangles in frontal and temporal cortex showed no correlation with the bulk aluminum concentration. Logistic regression analyses, which controlled for age and sex, did not influence outcome for any of the comparisons. The data show conclusively that in AD, bulk aluminum concentration is not increased in two cortical brain regions that are selectively vulnerable to the neuropathological changes associated with this disorder.

A cohort of elderly Norwegians dying in nursing homes in the Oslo region have been genotyped for the Apolipoprotein E (ApoE) gene. Alzheimer's disease (AD) cortical neuropathology and clinical evidence of dementia were used to assign cases without evidence of other confounding neuropathology. Senile plaque (SP) and neurofibrillary tangle (NFT) densities in frontal, temporal and parietal cortex were then correlated with ApoE genotype to determine any relationship between ApoE genotype and AD pathology. Comparisons with ApoE ε3, ε4 and ε2 allele dosage failed to show any significant effect on cortical SP densities in any cortical area. NFT densities were increased by ε4 allele dosage in the frontal cortex but not in other cortical regions. A reduction was seen in cortical NFT densities with ε2 allele, though again this was not consistently significant in any of the groups. The ε3 allele failed to show any consistent effect on cortical NFT densities. Assessment by individual genotypes showed ε23 < ε24 < ε33 < ε34 < ε44 which had highest cortical NFT densities in all areas. By genotype, SP densities were generally of the order ε24 < ε23 < ε33 < ε44 < ε34 though in none of the groups was this significant. Duration of disease showed no consistent effect on neuropathological burden. ApoE genotype may have an effect on determining whether individuals suffer from AD and the age at onset of disease but may only have a minimal effect on pathology burden.

Neuropathological changes in elderly residents of Oslo, Norway were characterised with respect to the cerebral substrates of dementia. Ninety-two brains were examined, representing 41% of all deaths occurring in 10 nursing homes during a 9-month period. The autopsy cohort showed a similar mean age (85 years) and sex ratio (73% female) and proportion of demented patients (75%) compared to all the patients resident in these homes who died during the same period. Clinical data was compiled retrospectively. Diagnosis was made using the CERAD protocol, and criteria for the diagnosis of Lewy body dementia. Lewy body formation was present in 20% and cerebral infarction in 21% of patients. In the demented group (69 patients) 90% fulfilled CERAD criteria for definite or probable Alzheimer's disease. Eight demented cases had absent neocortical neurofibrillary tangles and 6 other cases showed Lewy body dementia (9% of demented patients). A further 8 of these demented cases had brain stem Lewy bodies with only minimal cortical involvement. Thirteen cases (19% of the sample) had cerebral infarcts but these were considered to be clinically significant in only 4 (6%). In the non-demented patients (23) 4 patients had brain stem Lewy bodies and 6 had cerebral infarcts. Despite inclusion criteria biased towards the collection of Alzheimer's disease and normal patients, both Lewy body dementia (7%) and cerebral infarcts contributing to dementia (6%) were frequent.