Corpus callosum tissue loss and development of motor and global cognitive impairment: the LADIS study.

OBJECTIVE: To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly. METHODS: This study was based on the Leukoaraiosis and Disability (LADIS) study. Assessment of cognitive and motor functions and magnetic resonance imaging (MRI) were done at baseline and at a 3-year follow-up in nondemented elderly subjects. RESULTS: 328 of 639 LADIS subjects had MRIs at baseline and at the 3-year follow-up, which allowed for assessment of CC. Logistic regression revealed differential tissue loss rates in posterior CC in subjects converting to dementia, compared to nonconverters (p < 0.05). Anterior and posterior CC tissue loss was significantly correlated with self-perceived memory impairment in nonconverters (p < 0.05). CC tissue loss was also significantly associated with impaired single leg stance time (p < 0.01). CONCLUSION: The present longitudinal study on CC supports the role of callosal tissue loss in the development of global cognitive as well as motor impairment.

Apolipoprotein E (APOE) polymorphism influences serum APOE levels in Alzheimer's disease patients and centenarians.

Vascular factors may play a role in the etiology of Alzheimer's disease (AD) and increased serum apolipoprotein E (APOE) levels in AD could be of interest, as APOE concentration is associated with vascular disease. Aims of this study were to evaluate the influence of APOE genotype on serum APOE levels, and, secondly, to study serum APOE concentrations in relation to age and AD. APOE genotypes, serum total cholesterol, LDL cholesterol, HDL cholesterol, total cholesterol/HDL cholesterol ratio, triglycerides, and serum APOE were performed on 52 healthy centenarians, 49 AD patients, 45 age-matched controls, and 72 young healthy adults. In all study population a significant trend in reduction of serum APOE levels from APOE epsilon2- to epsilon4 carriers was observed. The difference in serum APOE levels among age groups significantly decreased in epsilon4 carriers only, including HDL cholesterol; no significant differences between AD patients and age-matched controls were found. In these highly selected populations, APOE genotype distribution strongly influences serum APOE concentration, not suggesting, at present, a possible role as a biochemical marker for AD, but only as a putative longevity factor.

Regional European differences in allele and genotype frequencies of low density lipoprotein receptor-related protein 1 polymorphism in Alzheimer's disease.

The low density lipoprotein receptor-related protein 1 (LRP1 gene) is a candidate gene for Alzheimer's disease (AD), because it is a ligand for proteins involved in AD pathogenesis, such as apolipoprotein E (APOE), alpha2-macroglobulin (A2M), amyloid precursor protein (APP), and is located on chromosome 12, within a region linked with AD. An association between a silent polymorphism (C/T) in exon 3 and late onset AD has been reported, with an increased frequency of the C allele, although with conflicting results. We examined this polymorphism in a cohort of 166 sporadic AD patients and 225 sex- and age-matched nondemented controls from Southern Italy. No statistically significant differences were found in LRP1 genotype and allele frequencies between the whole AD sample and controls, nor in early- and late-onset subsets of AD patients. No statistically significant differences in frequencies between LRP1 alleles and AD among APOE allele, age, or gender strata were found. Finally, comparing our results with the findings from other European populations, the LRP1 C allele frequency showed a statistically significant decreasing trend from Northern to Southern regions of Europe, with a concomitant increase in LRP1 T allele frequency, but in AD patients only. Finally, in the AD sample, a decreasing geographical trend from North to South of Europe was found for LRP1 CC genotype, and an inverse trend for LRP1 CT genotype frequency. We suggest that these regional variations in LRP1 genotype and allele frequencies in AD could be related to the different patterns of association between this polymorphism and the disease in various European studies.