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Byline: Giovanni Savettieri (1), Virginia Andreoli (2), Simona Bonavita (3), Rita Cittadella (2), Carlo Caltagirone (4), Maria Carolina Fazio (5), Paolo Girlanda (5), Francesco Pira (6), Maria Liguori (7), Giancarlo Logroscino (8), Alessandra Lugaresi (9), Ugo Nocentini (4), Arturo Reggio (6), Giuseppe Salemi (1), Paolo Serra (2), Gioacchino Tedeschi (3), Lucia Toma (9), Maria Trojano (7), Paola Valentino (10), Aldo Quattrone (2,10,11) Keywords: multiple sclerosis; APOE polymorphism; APOE promoter; MS progression Abstract: Objective: To investigate the association between apolipoprotein E (APOE) polymorphisms and the progression of MS. Methods: We investigated 428 subjects affected by clinically defined MS, with a disease duration of at least three years. We collected data concerning the age at onset of MS, clinical type, disease duration and disability according to the expanded disability status scale (EDSS). We also calculated the progression index (PI) to evaluate disease progression. APOE genotyping and the --491 A/T polymorphism of the APOE promoter were determined. Results: No association was observed between the APOE [epsilon]4 allele and clinical characteristics of our study population. We also investigated the --491 A/T APOE promoter polymorphism in 236 MS subjects and did not find any association between the --491 A/T polymorphism and the selected clinical variables. Conclusions: In our population the APOE [epsilon]4 allele and the --491 A/T APOE promoter polymorphism are not associated with a more rapid course of MS. Author Affiliation: (1) Institute of Neuropsychiatry, University of Palermo, Palermo, Italy (2) Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone (Cosenza), Italy (3) Dept. of Neurological Sciences, 2nd University of Naples, Naples, Italy (4) Cattedra di Neurologia and I.R.C.C.S., Fondazione 'S. Lucia', University of Rome 'Tor Vergata', Rome, Italy (5) Dept. of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy (6) Dept. of Neurological Sciences, University of Catania, Catania, Italy (7) Dept. of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy (8) Dept. of Neurology, Ospedale Miulli, Bari, Italy (9) Dept. of Oncology &amp Neuroscience, University of Chieti 'Gabriele d'Annunzio', Chieti, Italy (10) Institute of Neurology, University Magna Graecia, Catanzaro, Italy (11) Clinica Neurologica, Policlinico Mater Domini, Via T. Campanella, 88100, Catanzaro, Italy Article History: Received Date: 10/10/2002 Accepted Date: 08/05/2003

Alzheimer's disease (AD) is a devastating disease mainly afflicting elderly people, characterized by decreased cognition, loss of memory, and eventually death. Although risk and deterministic genes are known, major genetics research programs are underway to gain further insights into the inheritance of AD. In the last years, in particular, new developments in genome-wide scanning methodologies have enabled the association of a number of previously uncharacterized copy number variants (CNVs, gain or loss of DNA) in AD. Because of the exceedingly large number of studies performed, it has become difficult for geneticists as well as clinicians to systematically follow, evaluate, and interpret the growing number of (sometime conflicting) CNVs implicated in AD. In this review, after a brief introduction of this type of structural variation, and a description of available databases, computational analyses, and technologies involved, we provide a systematic review of all published data showing statistical and scientific significance of pathogenic CNVs and discuss the role they might play in AD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on phenotypic variation of dominant optic atrophy and deafness due to a novel OPA1 mutation that was published in previous issue.

Several pathogenetic factors seem to contribute to the development of Alzheimer's disease (AD). Some data point to a role for traumatic brain injury (TBI), but this suggestion is not universally supported. Mayeux et al. have shown that TBI increases the risk of AD, but only through a synergistic relationship with apolipoprotein epsilon (Apo E) 4. We present the results of a cross-sectional and longitudinal study of the relationship between these factors, conducted in northern and southern Italy. We studied 337 consecutive patients with probable AD and 63 subjects with mild cognitive impairment (MCI). Information concerning head injuries was collected by interview of informants and review of medical records. Twenty-one patients with AD and 9 with MCI were found to have a history of TBI with loss of consciousness. AD and MCI patients with a history of TBI, compared with control groups matched for age, sex, education and degree of mental impairment, showed more marked depressive and behavioural disturbances (Global Deterioration Scale and Neuropsychiatric Inventory, p<0.05). Six- and 12-month follow up of both groups did not show significant differences in the rate of progression of cognitive changes. A high frequency of Apo E 4 was detected in the patients with TBI and cognitive impairment (40.5% in the AD and 11% in the MCI subgroups). The distribution of the epsilon 4 allele in our control group was 4%, comparable to that found in the Italian population. Distribution of the above parameters was similar in patients from northern and southern Italy. The higher frequency of TBI and Apo E 4 genotype among AD and MCI patients confirms the synergistic interaction of environmental and genetic factors in the development of dementia. Our data do not suggest that the presence of these two factors influences the clinical presentation or the course of the disease.