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Alzheimer's disease (AD) represents the most prevalent manifestation of the cognitive disorders in the elderly. The dramatic nature and the economic burden of the disease make AD a worl-wide problem. This paper reviews the genetic factors which explain the pathogenesis of AD, i.e., mutations of the genes encoding the amyloid precursor protein (APP), presenilin 1 (PS-1) and 2 (PS-2). Moreover, the polymorphism of the ApoE gene and the mutations of the hemochromatosis gene (HFE) are discussed. HFE mutations may anticipate the clinical manifestation of AD. The epigenetic factors related to AD are also discussed

Apolipoprotein E genotypes were determined in 30 healthy elderly controls, 42 patients with Alzheimer's disease, 13 subjects with vascular dementia and 31 individuals with Down's syndrome. The frequency of epsilon4 allele carriers was significantly increased in the Alzheimer's disease group (chi(2)=4.918, P0.05) but also in the vascular dementia subjects (P0.01, Fisher's exact test). The established relationship between genotype and age at onset of Alzheimer's disease was not statistically significant in these data. Frequencies of the genotypes in the Down's syndrome group did not differ from those of controls. The results obtained in this sample of the Italian population suggest that the apolipoprotein E genotype may be of limited use in the differential diagnosis of dementia.

In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 +/- 6.0 years versus 76.6 +/- 5.8 years of those who were homozygous for the wild-type allele (p = 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged < 70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70-80 years, and 0.04 in those aged more than 80 years, The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals. (C) 2001 Elsevier Science Inc. All rights reserved.

A rapid and specific diagnostic test for Alzheimer’s disease (AD), the prevalent cause of dementia in the elderly, is currently unavailable. The aim of this study was to verify the validity of the recently proposed ‘Eye Test’ in the identification of AD patients, based on their supposed greater mydriatic response to cholinergic antagonists. We tested the pupillary response to the instillation of 0.01% tropicamide in 48 subjects: 15 patients with probable or possible Alzheimer’s disease, five patients with vascular dementia (VD), 16 elderly controls (EC) and 12 young controls (YC). Mean pupil dilation in the treated eye at 30 and 40 min after drops instillation was not significantly different among the four groups. The mean change in anisocoria at 30 min was significantly greater in the AD group (0.90 mm, S.D. 0.83) than in the YC group (0.21 mm, S.D. 0.46), but no significant difference was found among the AD group, the EC group and the VD group. Our results, therefore, do not support the potential usefulness of the pupillary response to dilute tropicamide for identifying individuals with AD.

The analysis of variance for repeated measures was utilized, using the change of pupil diameter from baseline in the eye treated with tropicamide as a dependent variable. In a second analysis, we considered the change in anisocoria (difference between the change of pupil diameter in the treated eye and that in the contralateral eye) as a dependent variable, using the