%0 Journal Article %J J Alzheimers Dis %D 2018 %T Altered Expression of Circulating Cdc42 in Frontotemporal Lobar Degeneration. %A Saraceno, Claudia %A Catania, Marcella %A Paterlini, Anna %A Fostinelli, Silvia %A Ciani, Miriam %A Zanardini, Roberta %A Binetti, Giuliano %A Di Fede, Giuseppe %A Caroppo, Paola %A Benussi, Luisa %A Ghidoni, Roberta %A Bolognin, Silvia %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Brain %K Case-Control Studies %K cdc42 GTP-Binding Protein %K Female %K Frontotemporal Lobar Degeneration %K Humans %K Male %K Middle Aged %X

The term frontotemporal lobar degeneration (FTLD) defines a group of heterogeneous conditions histologically characterized by neuronal degeneration, inclusions of various proteins, and synaptic loss. However, the molecular mechanisms contributing to these alterations are still unknown. As the Rho-GTPase family member Cell division cycle 42 (Cdc42) plays a key role in the regulation of actin cytoskeleton dynamics and spine formation, we investigated whether Cdc42 protein levels were altered in the disease. Cdc42 was increased in the frontal cortex of FTLD patients compared to age-matched controls, but also in Alzheimer's disease (AD) patients included in the data-set. On the other hand, the pool of circulating Cdc42 in the plasma was altered in FTLD but not in AD patients. Interestingly, the stratification of the FTLD patients according to the different clinical variants showed a specific decrease of Cdc42 expression in the behavioral subgroup. This data support a role of Cdc42 in FTLD and specifically in the behavioral variant.

%B J Alzheimers Dis %V 61 %P 1477-1483 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29376863?dopt=Abstract %R 10.3233/JAD-170722 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Translational Research in Alzheimer's and Prion Diseases. %A Di Fede, Giuseppe %A Giaccone, Giorgio %A Salmona, Mario %A Tagliavini, Fabrizio %X

Translational neuroscience integrates the knowledge derived by basic neuroscience with the development of new diagnostic and therapeutic tools that may be applied to clinical practice in neurological diseases. This information can be used to improve clinical trial designs and outcomes that will accelerate drug development, and to discover novel biomarkers which can be efficiently employed to early recognize neurological disorders and provide information regarding the effects of drugs on the underlying disease biology. Alzheimer's disease (AD) and prion disease are two classes of neurodegenerative disorders characterized by incomplete knowledge of the molecular mechanisms underlying their occurrence and the lack of valid biomarkers and effective treatments. For these reasons, the design of therapies that prevent or delay the onset, slow the progression, or improve the symptoms associated to these disorders is urgently needed. During the last few decades, translational research provided a framework for advancing development of new diagnostic devices and promising disease-modifying therapies for patients with prion encephalopathies and AD. In this review, we provide present evidence of how supportive can be the translational approach to the study of dementias and show some results of our preclinical studies which have been translated to the clinical application following the 'bed-to-bench-and-back' research model.

%B J Alzheimers Dis %V 62 %P 1247-1259 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29172000?dopt=Abstract %R 10.3233/JAD-170770 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Genetic Counseling and Testing for Alzheimer's Disease and Frontotemporal Lobar Degeneration: An Italian Consensus Protocol. %A Bocchetta, Martina %A Mega, Anna %A Bernardi, Livia %A Di Maria, Emilio %A Benussi, Luisa %A Binetti, Giuliano %A Borroni, Barbara %A Colao, Rosanna %A Di Fede, Giuseppe %A Fostinelli, Silvia %A Galimberti, Daniela %A Gennarelli, Massimo %A Ghidoni, Roberta %A Piaceri, Irene %A Pievani, Michela %A Porteri, Corinna %A Redaelli, Veronica %A Rossi, Giacomina %A Suardi, Silvia %A Babiloni, Claudio %A Scarpini, Elio %A Tagliavini, Fabrizio %A Padovani, Alessandro %A Nacmias, Benedetta %A Sorbi, Sandro %A Frisoni, Giovanni B %A Bruni, Amalia C %K Alzheimer Disease %K Amyloid beta-Peptides %K Consensus %K Female %K Follow-Up Studies %K Frontotemporal Lobar Degeneration %K Genetic Counseling %K Genetic Testing %K Humans %K Italy %K Male %K Peptide Fragments %K Psychiatric Status Rating Scales %X

BACKGROUND: Genetic testing of familial Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is attracting interest thanks to innovative primary prevention clinical trials and increased request for information by at-risk individuals. However, ethical, social, and psychological implications are paramount and genetic testing must be supported by structured genetic counseling. In Italy, practice parameters and guidelines for genetic counseling in dementia are not available.

OBJECTIVE: To develop a nationally harmonized protocol for genetic counseling and testing of familial AD and FTLD.

METHODS: Activities were carried out in the context of the Italian Dominantly Inherited Alzheimer's and Frontotemporal Network (IT-DIAfN) project, a national network of centers of excellence with expertise in managing patients with familial AD and FTLD. A survey of the literature on genetic counseling protocols and guidelines was conducted. Local protocols for genetic counseling were surveyed. Differences and commonalities among protocols were identified and discussed among project partners. Consensus was reached following implicit aggregation methods.

RESULTS: Consensus was reached on a protocol for patients with clinically diagnosed familial AD or FTLD and a distinct protocol for their at-risk relatives. Genetic counseling should be provided by a multidisciplinary team including a geneticist, a neurologist/geriatrician, and a psychologist/psychiatrist, according to the following schedule: (i) initial consultation with tailored information on the genetics of the dementias; (ii) clinical, psychological, and cognitive assessment; if deemed appropriate (iii) genetic testing following a structured decision tree for gene mutation search; (iv) genetic testing result disclosure; (v) psychological support follow-up.

CONCLUSION: This genetic counseling protocol provides Italian centers with a line of shared practice for dealing with the requests for genetic testing for familial AD and FTLD from patients and at-risk relatives, who may also be eligible participants for novel prevention clinical trials.

%B J Alzheimers Dis %V 51 %P 277-91 %8 2016 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26901402?dopt=Abstract %R 10.3233/JAD-150849