No abstract

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios (ORs) alone are insufficient to assess these risks. We calculated AD lifetime risk in 7,351 cases and 10,132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68% and 35 % for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age- groups clearly demonstrates that APOE4 is a risk factor not only for late- onset but for early- onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.

The present functional data on large populations support the 'transitional hypothesis' of a shadow zone across normality, pre-clinical stage of dementia (MCI), and AD.

The study aimed at mapping (i) the distributed electroencephalographic (EEG) sources specific for mild Alzheimer's disease (AD) compared to vascular dementia (VaD) or normal elderly people (Nold) and (ii) the distributed EEG sources sensitive to the mild AD at different stages of severity. Resting EEG (10-20 electrode montage) was recorded from 48 mild AD, 20 VaD, and 38 Nold subjects. Both AD and VaD patients had 24-17 of mini mental state examination (MMSE). EEG rhythms were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG sources were modeled by low resolution brain electromagnetic tomography (LORETA). Regarding issue i, there was a decline of central, parietal, temporal, and limbic alpha 1 (low alpha) sources specific for mild AD group with respect to Nold and VaD groups. Furthermore, occipital alpha 1 sources showed a strong decline in mild AD compared to VaD group. Finally, distributed theta sources were largely abnormal in VaD but not in mild AD group. Regarding issue ii, there was a lower power of occipital alpha 1 sources in mild AD subgroup having more severe disease. Compared to previous field studies, this was the first investigation that illustrated the power spectrum profiles at the level of cortical (macroregions) EEG sources in mild AD patients having different severity of the disease with respect to VaD and normal subjects. Future studies should evaluate the clinical usefulness of this approach in early differential diagnosis, disease staging, and therapy monitoring.