Paolo Forleo

ApoE allele frequencies in Italian sporadic and familial Alzheimer's disease

Recent studies have provided evidence of association of apolipoprotein E (ApoE) epsilon 4 allele and late onset familial and sporadic Alzheimers disease (AD). Epidemiological studies have established allelic variation at the ApoE locus. We have analyzed the ApoE gene polymorphism in a sample of 446 Italian subjects. Our data confirm a significant association between epsilon 4 allele and sporadic AD. The frequency of epsilon 4 allele in early onset familial AD patients was comparable to control values suggesting that epsilon 4 allele does not represent a risk factor for early onset familial AD (EOFAD). Moreover, we found a not previously reported association between ApoE epsilon 2 allele and sporadic AD and EOFAD.

Technical limits in transcranial Doppler recording: Inadquate acoustic windows

Transcranial Doppler (TCD) is a technique that evaluates blood flow velocity in intracranial vessels. It uses a 2-MHz probe and a Doppler signal analyzer. Absence of an acoustic window is a considerable problem for clinical utilization of TCD because cerebrovascular patients are frequently elderly. Previous reports suggest a higher prevalence of inadequate temporal acoustic window (TAW) in aged subjects and in females. A consecutive series of 624 subjects (376 males and 248 females, age range 2-86 y) were evaluated by standard TCD examination, to assess the contemporary absence of any signal corresponding to insonated basal arteries, defined as inadequate acoustic window. The rate of inadequate TAW was 8.2%, that of inadequate occipital acoustic window (OAW) was 9.0%. Prevalence of inadequate TAW was higher in females than in males, and OAW was higher in males than in females. Influence of aging on the presence of inadequate acoustic window is confirmed for temporal, but not for the occipital window. Different anatomical characteristics of the 2 regions could explain the different prevalence of TAW and OAW.

ApoE genotype and familial Alzheimer's disease: a possible influence on age of onset in APP717 Val-->Ile mutated families.

Recent studies have shown a genetic association of the apolipoprotein E (ApoE) epsilon 4 allele with late onset familial and sporadic Alzheimers disease (AD). In this study we analysed the possible association of the genetic polymorphism of the ApoE gene with age of onset in Italian familial Alzheimers disease (FAD) families including two early onset familial Alzheimers (EOFAD) families with the APP717 Val-->Ile mutation in the amyloid precursor protein (APP) gene on chromosome 21. In none of the FAD families analysed was there a significant effect of the ApoE genotype on the age of onset with the exception of one of the two mutated EOFAD families in which the epsilon 2 allele delayed the age of onset.

Association between 5-HT2A receptor polymorphism and psychotic symptoms in Alzheimer’s disease

Abstract Background: The aim of this study is to analyze the segregation of the 102T/C polymorphism in the serotonin 2A receptor gene in patients affected by sporadic and familial Alzheimer’s disease (FAD) with and without psychotic symptoms. Methods: The polymorphism was analyzed in 275 subjects. A semistructured interview was used to obtain information about delusions, hallucinations, and other specific behavioral signs occurring during the disease. Results: Fifty-two percent of AD patients with psychotic symptoms were homozygous for the C102 allele, as compared with 6.9% of AD patients without psychosis. Similarly, the C102/C102 genotype was significantly more frequent in FAD patients with psychosis than in FAD patients without (46.5% vs. 7.8%). Conclusions: Our data strongly confirm and extend to FAD previous studies suggesting that the genetic variation at this locus is associated with prominent psychotic features in AD and that the 102C allele could play an important role in late-onset AD.

Guidelines for the diagnosis of dementia and Alzheimer's disease

SIN DOCUMENT*The Dementia Study Group is co-ordinated by Sandro Sorbi andincludes: Margherita Alberoni, Milan; Pasquale Alfieri, SommaVesuviana (NA); Serena Amici, Perugia; Daniele Antana, Rome;Ildebrando Appollonio, Monza (MI); Stefano Avanzi,Castelgoffredo (MN); Antonella Bartoli, Pescara; BrunoBergamasco, Turin; Laura Bracco, Florence; Amalia Bruni,Lamezia Terme (CZ); Orso Bugiani, Milan; Paolo Caffarra, Parma;Carlo Caltagirone, Rome; Antonio Carolei, L’Aquila; Anna RosaCasini, Rome; Luciana Ciannella, Benevento; Antonietta Citterio,Pavia; Antonio Daniele, Rome; Graziella D’Achille, Isernia;Giuseppe Del Curatolo, Grosseto; Grazia Dell’Agnello, Pisa;Daniele Durante, Parma; Elisabetta Farina, Milan; Patrizia Ferrero,Turin; Paolo Forleo, Florence; Guido Gainotti, Rome; PaoloGabriele, Cassino (FR); Emanuela Galante, Castelgoffredo (MN);Virgilio Gallai, Perugia; Roberto Gallassi, Bologna; MaddalenaGasparini, Milan; Bernardino Ghetti, Indianapolis (USA); GiorgioGiaccone, Milan; Floriano Girotti, Milan; Luigi Grimaldi, Milanand Caltanisetta; Serenella Grioli, Catania; Bianca MariaGuarnieri, Pescara; Stefano Grottoli, Fossombrone (PS); FrancescoIemolo, Ragusa; Stefania Latorraca, Florence; Francesco Le Pira,Catania; Gian Luigi Lenzi, Rome; Sebastiano Lorusso, Rimini;Claudio Mariani, Milan; Gabriella Marcon, Udine; VincenzoMascia, Carbonia (CA); Simonetta Mearelli, L’Aquila; MariaMorante, Senigallia (AN); Michela Morbin, Milan; MassimoMusicco, Segrate (MI); Ettore Nardelli, Verona; Paolo Nichelli,Modena; Alessandro Padovani, Brescia; Marco Paganini, Florence;Roberta Pantieri, Bologna; Pietro Parisen, Vicenza; LucillaParnetti, Perugia; Bruno Passerella, Brindisi; Carla Pettenati, Rho(MI); Silvia Piacentini, Florence; Federico Piccoli, Palermo; CarloPiccolini, Perugia; Gilberto Pizzolato, Padova; LeandroProvinciali, Ancona; Nicola Pugliese, Salerno; Francesco Redi,Arezzo; Rosa Maria Ruggieri, Palermo; Umberto Ruggiero,Naples; Marco Saetta, Siracusa; Rudolf Schoenuber, Bolzano;Maria Caterina Silveri, Rome; Sandro Sorbi, Florence; GiuseppeSorrentino, Naples; Patrizia Sucapane, L’Aquila; Andrea Stracciari,Bologna; Massimo Tabaton, Genova; Fabrizio Tagliavini, Milan;Vito Toso, Vicenza; Francesco Valluzzi, Putignano Noci (BA)S. Sorbi ( )Department of Neurological and Psychiatric SciencesUniversity of FlorenceViale Morgagni 85, I-50131 Florence, Italy

A presenilin-1 mutation (Leu392Pro) in a familial AD kindred with psychiatric symptoms at onset

Missense mutations in the presenilin genes are implicated in the majority of early-onset familial AD (EOFAD) cases. Presenilin 1 (PS-1) is a multispanning membrane protein composed of 467 amino acids, containing six to nine transmembrane helical domains and a large hydrophilic loop between domains six and seven. To date, more than 50 missense mutations1 and a splice site mutation in PS-1 have been found to cosegregate with EOFAD. Common phenotypic features of presenilin-1 linked families include onset of memory disturbances before age 50 years, shorter disease duration, and the presence of myoclonus and generalized seizures. We have performed a clinical and genetic screening in order to search for additional missense presenilin mutations in families with EOFAD, identifying a new family with a previously undescribed missense mutation in exon 11 leading to a Leu to Pro substitution at codon 392. This mutation was not detected in 50 unrelated subjects, indicating that this is not a common polymorphism. The members of this kindred belong to a three-generation family from central Italy ( figure). The proband, (III-1), a 38-year-old man, …

Double-blind, crossover, placebo-controlled clinical trial with L-acetylcarnitine in patients with degenerative cerebellar ataxia.

Despite the different genetic defects underlying degenerative ataxias, it has been suggested that mitochondrial energy production and antioxidative metabolism dysfunction may be common biochemical alterations related to these diseases. Acetylcarnitine, a cholinomimetic substance, is involved in oxidative metabolism and is a potential source of acetyl groups for the synthesis of acetylcholine in the mammalian brain. To determine whether treatment with L-acetylcarnitine may improve some clinical conditions of patients with ataxia, a double-blind crossover study with L-acetylcarnitine was performed in 24 patients with degenerative cerebellar diseases. Patients were selected from an ongoing prospective follow-up study at the Department of Neurology at the University of Florence, Italy. Each treatment phase with L-acetylcarnitine or placebo lasted 6 months, after which patients were crossed over to the other treatment phase. Ataxia was documented and quantified with use of a clinical score. After the trial, we observed a statistically significant improvement of some symptoms and a slow progression of the disease in both groups of patients.

Presenilin-1 gene intronic polymorphism in sporadic and familial Alzheimer's disease

A recent observation has shown a genetic association between an intronic polymorphism in the Presenilin-1 (PS-1) gene and late onset Alzheimers disease (AD). The homozygosity of the 1 allele in the PS-1 gene was associated with a doubling of the risk for late onset AD. However, contrasting results have been published. We analyzed the distribution of the PS-1 intronic polymorphism in patients with sporadic AD and in seven familial AD (FAD) families carrying pathogenetic mutations in the amyloid precursor protein (APP) and Presenilin (PS-1 and PS-2) genes. Significant differences in PS-1 allele frequencies were observed in the Presenilin genes mutated families but not in late onset AD patients and in APP mutated families.

Alzheimer's Disease and Apolipoprotein E in Italya

Recent studies have provided evidence of association of apolipoprotein E (ApoE) ε4 allele and late onset familial and sporadic Alzheimers disease (AD). Epidemiological studies have established allelic variation at the ApoE locus. We have analyzed the ApoE gene polymorphism in a sample of 416 Italian subjects. Our data confirm a significant association between ε4 allele and sporadic AD. The frequency of ε4 allele in early onset familial AD patients was comparable to control values suggesting that ε4 allele does not represent a risk factor for early onset familial AD (EOFAD). Moreover, we found a not‐previously reported association between ApoE ε2 allele and sporadic AD and EOFAD. We included in this study two EOFAD families with the APP717 Val → Ile mutation in the Amyloid Precursor Protein (APP) gene on chromosome 21.

Genetic risk factors in familial Alzheimer's disease

In the last 10 years significant progress has been made to describe and identify the underlying biological mechanisms that cause the different manifestation of Alzheimers disease. Since the first report of a possible locus on chromosome 21 in a small group of families with early onset familial Alzheimers disease (FAD), considerable progress has been made. Results from linkage analysis and gene sequencing has provided evidence that a minority of early onset FAD families develops the disease as a result of mutations in the gene coding for the Abeta-amyloid precursor protein, and that mutations in presenilin 1 and 2 genes account for a larger subgroup of early onset families. Several other early onset FAD families are clearly not linked to any of these loci, suggesting that other genetic risk factors may exist. Recent genome-wide scanning studies have revealed the existence of a new locus on chromosome 12, which, together with inheritance of the epsilon4 allele of apolipoprotein E gene, on chromosome 19, represent the most important genetic factors associated with an increased risk of developing the disease in late onset FAD families.