Alzheimer Disease: Musicco M

Caltagirone C, Bianchetti A, Di Luca M, Mecocci P, Padovani A, Pirfo E, Scapicchio P, Senin U, Trabucchi M, Musicco M, Anonymous00252. · Fondazione IRCCS, Santa Lucia, Università Tor Vergata, Rome, Italy. · Drugs Aging. · Pubmed #16506439 No free full text.

Abstract: A committee of experts from the Italian Association of Psychogeriatrics compiled the following report, which was then approved by a Steering Committee (comprising 20 specialists in neurology, psychiatry or geriatrics) from the Association and by two Alzheimer associations representing patients and families: the Italian Association for Alzheimer's Disease and the Italian Federation for Alzheimer's Disease. The report is based on a comprehensive review of the scientific literature on the treatment of Alzheimer's disease, discusses methodological aspects of dementia management, and details the limitations of current therapies. These guidelines are, in general, consistent with the principles of evidence-based medicine; however, for some controversial or poorly investigated issues, the guidelines integrate scientific evidence with experience and opinions from experts working in the clinical setting. In particular, the clinical experience of experts has been used to define recommendations for starting and interrupting pharmacotherapy, and to critically review evidence about the efficacy of non-pharmacological interventions. The principal pharmacotherapeutic interventions covered in the guidelines are acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and memantine. The main non-pharmacological interventions reviewed are memory training, reality orientation therapy, and combined non-pharmacological interventions. Other issues covered are opportunities for Alzheimer's disease prevention, various modalities of care, and the treatment of comorbidities.

Rao KS, Hegde ML, Anitha S, Musicco M, Zucca FA, Turro NJ, Zecca L. · Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570020, India. · Prog Neurobiol. · Pubmed #16682109 No free full text.

Abstract: Alzheimer's disease (AD) and Parkinson's disease (PD) share several pathological mechanisms. The parallels between amyloid beta (Abeta) in AD and alpha-synuclein in PD have been discussed in several reports. However, studies of the last few years show that Abeta also shares several important characteristics with neuromelanin (NM), whose role in PD is emerging. First, both molecules accumulate with aging, the greatest risk factor for AD and PD. Second, in spite of their different structures, Abeta and NM have similar characteristics that could also lead to neuroprotection. Metals are required to catalyze their formation and they can bind large amounts of these metals, generating stable complexes and thus playing a protective role against metal toxicity. Moreover, they may be able to remove toxic species such as oligopeptides and excess cytosolic dopamine. Third, both Abeta and NM have been implicated in parallel aspects of the neuronal death that underlies AD and PD, respectively. For example, both molecules can activate microglia, inducing release of toxic factors such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO). A careful analysis of these parallel effects of Abeta and NM, including their seemingly paradoxical ability to participate in both cell death and protection, may lead to an improved understanding of the roles of these molecules in neurodegeneration and also provide insights into possible parallels in the pathological mechanisms underlying AD and PD.

Musicco M, Pettenati C, Caltagirone C. · Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Via Fratelli Cervi 93, 20090 Segrate, Milan, Italy. · Ann Ist Super Sanita. · Pubmed #16037656 links to  free full text

Abstract: The efficacy of medical interventions is their capacity of inducing positive modifications of the natural history of diseases. The natural history of dementia is marked by specific events related to the cognitive and functional decline, but their occurrence is poorly predictable in individual patients being highly variable from patient to patient. For this reason it is difficult that the modest efficacy of available interventions for dementia, or their entity measured by clinical scales, may be perceived in clinical practice or in observational studies. Moreover in randomized clinical studies, the effect of this variability, in analogy to misclassification of exposition and/or disease in case control or cohort epidemiological studies, is that of an underestimation of the true efficacy of interventions.

Musicco M, Sorbi S, Bonavita V, Caltagirone C, Anonymous00322. · Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, I-20090 Segrate, Milan, Italy. · Neurol Sci. · Pubmed #15624087 No free full text.

Abstract: The objective of this study was to verify the adherence of Italian family physicians and neurologists to the Guidelines on Diagnosis of Dementia of the Italian Society of Neurology. A multicentre survey was carried out, in 72 neurological centres. The centres included at least 15 consecutive subjects suspected of having a dementia. The adherence of family physicians to the guidelines was poor. Neurologists performed a complete neuropsychological evaluation in a minority of the cases. Patients who had a decrease of Mini Mental Status Examination scores after six months higher than or equal to 4 were more represented among those patients for whom one or more recommendations were not respected. In Italy the adherence to the Guidelines on Diagnosis of Dementia and AlzheimerValidation studys Disease of the Italian Society of Neurology is very poor for family physicians (GPs) and satisfactory, albeit improvable, on the part of neurologists. Respect for the guidelines might improve the outcome of patients with dementia.

Poli M, Gatta LB, Lovati C, Mariani C, Galimberti D, Scarpini E, Biunno I, Musicco M, Dominici R, Albertini A, Finazzi D. · Section of Chemistry, Faculty of Medicine, University of Brescia, viale Europa 11, 25123 Brescia, Italy. · Neurobiol Aging. · Pubmed #17466415 No free full text.

Abstract: The gamma-secretase complex is a multimeric aspartyl protease which plays a pivotal role in the production of amyloid beta-peptide, the main component of senile plaques in Alzheimer's disease (AD). APH-1a and APH-1b have been recently identified as important subunits of the gamma-secretase complex. We previously studied sequence variations in both genes and their association with AD in a small Italian population. The rare polymorphism c + 651T > G in APH-1b showed a possible interaction with the Apolipoprotein E (APOE) epsilon4 allele in the AD population sample. We extended our genetic analysis to 449 AD patients and 435 controls and, in AD cases, we found a significant interaction (P=0.001) between the allelic variants in the two genes, resulting in a marked increase of the relative risk for AD (OR=28.6). Despite the amino acid substitution does not seem to modify either the intracellular localization or the half-life of APH-1b protein, these data suggest that a cooperative mechanism involving APOE and APH-1b plays a role in the susceptibility to develop AD.

Tomaiuolo F, Scapin M, Di Paola M, Le Nezet P, Fadda L, Musicco M, Caltagirone C, Collins DL. · IRCCS Fondazione Santa Lucia, Università di Roma Tor Vergata, Roma, Italia. · Dement Geriatr Cogn Disord. · Pubmed #17127820 No free full text.

Abstract: BACKGROUND/AIMS: Differences in the gross shape of the corpus callosum (CC) and its subregional areas were investigated on brain MRI of patients with probable Alzheimer's disease (AD) and age- and gender-matched healthy normal control subjects. The AD patients differed from the normal control subjects in terms of a more convex shape and a reduced area of the CC. METHODS: As for the comparisons of the subregional areas of the CC, we adapted a splitting method which takes into account the modification of the global shape of the CC, and we implemented it by normalizing the CC, to avoid the bias introduced by the observed callosal shape variability. RESULTS: The application of this method unveiled that the regional CC reductions were located in the anterior and posterior third of the CC, i.e. where small myelinated fibers are more frequent. None of the neuropsychological scores collected at the time of the MRI investigation of AD could predict a regional and/or overall callosal area reduction. The only measure that correlated with area of the isthmus of the CC was the MMSE that was administered to all participants. CONCLUSIONS: This latter result may be used as an in vivo indicator of the progress of neocortical disintegration in AD.

Saltini G, Dominici R, Lovati C, Cattaneo M, Michelini S, Malferrari G, Caprera A, Milanesi L, Finazzi D, Bertora P, Scarpini E, Galimberti D, Venturelli E, Musicco M, Adorni F, Mariani C, Biunno I. · Department of Sciences and Biomedical Technologies, University of Milan Via F.lli Cervi 93, 20090 Segrate-Milan, Italy. · Neurosci Lett. · Pubmed #16412574 No free full text.

Abstract: Alzheimer's disease (AD) is considered to be a conformational disease arising from the accumulation of misfolded and unfolded proteins in the endoplasmic reticulum (ER). SEL1L is a component of the ER stress degradation system, which serves to remove unfolded proteins by retrograde degradation using the ubiquitin-proteosome system. In order to identify genetic variations possibly involved in the disease, we analysed the entire SEL1L gene sequence in Italian sporadic AD patients. Here we report on the identification of a new polymorphism within the SEL1L intron 3 (IVS3-88 A>G), which contains potential binding sites for transcription factors involved in ER-induced stress. Our statistical analysis shows a possible role of the novel polymorphism as independent susceptibility factor of Alzheimer's dementia.

Zatta P, Zambenedetti P, Musicco M, Adorni F. · CNR-Institute for Biomedical Technologies, Metalloproteins Unit, Department of Biology, University of Padua, Italy. · J Alzheimers Dis. · Pubmed #16308479 No free full text.

Abstract: Frontotemporal dementia regards a group of presenile progressive neurodegenerative form of dementias which includes Pick's disease, corticobasal degeneration, frontotemporal dementia with motor neuron disease, frontal lobe degeneration, dementia-parkinsonism-amyotrophy complex, familial non-specific dementia mapping to chromosome 3, non-Alzheimer degenerative dementia lacking distinctive histological features as well as a number other infrequent syndromes with dementia and focal neurological signs. The aim of this study was to investigate the regional distribution of metallothionein-I-II, an ubiquitary group of buffering proteins, in cases of frontotemporal dementia. The aim of the present study was to study the metallothionein-I-II expression in relationship to the expression in astrocytes of glial fibrillary acidic protein (GFAP) as we have already done in previous studies of Alzheimer's and Binswanger's diseases [31,32]. Our findings indicate that metallothionein-I-II expression in the most affected areas is likely to be regionally distinct and layer-dependent, in that it is highest in the deep layers of the frontotemporal cortex and the allocortex (hippocampus) while insignificantly immunopositive in the occipital cortex. In addition, the potential use of metallothionein-I-II as a new pharmacological approach to contrast some deleterious aspects of this disease has been also discussed.

Zambenedetti P, De Bellis G, Biunno I, Musicco M, Zatta P. · Pathology Division and Brain Bank, General Hospital, Dolo-Venice, Italy. · J Alzheimers Dis. · Pubmed #14757931 No free full text.

Abstract: Several gene mutations are associated with an increased risk of Alzheimer's disease. Previous studies reported higher transferrin C2 allele frequencies in Alzheimer's disease compared with normal controls. However, potential interactions between transferrin C2 and APOE (epsilon 4), have not been extensively investigated and have been the subject of controversial reports from several laboratories. We have carried out a case-control study on the association between Alzheimer's disease and transferrin C2 and APOE epsilon 4 alleles. epsilon 4 allele was associated with a four fold increase in the risk of disease, and transferrin C2 allele was significantly associated with Alzheimer's disease only in epsilon 4 negative subjects. These results suggest that apoE and transferrin may be part of a complex mechanism in the pathogenesis of Alzheimer's disease.