Neural correlates of altered insight in frontotemporal dementia: a systematic review.

Altered insight into disease or specific symptoms is a prominent clinical feature of frontotemporal dementia (FTD). Understanding the neural bases of insight is crucial to help improve FTD diagnosis, classification and management. A systematic review to explore the neural correlates of altered insight in FTD and associated syndromes was conducted.

Association of the New Variant Tyr424Asp at TBK1 Gene with Amyotrophic Lateral Sclerosis and Cognitive Decline.

A new risk gene associated with amyotrophic lateral sclerosis (ALS) has recently been identified: the Tank-binding kinase 1 (TBK1) gene. Up to now, 90 TBK1 variants have been described in ALS patients with or without frontotemporal dementia (FTD), thus making TBK1 the third or fourth most frequent genetic cause of ALS and FTD. A point mutation analysis in a cohort of 69 Italian ALS patients was performed in order to analyze the frequency of TBK1 mutations and the correlation with clinical phenotypes.

The novel PSEN1 M84V mutation associated to frontal dysexecutive syndrome, spastic paraparesis, and cerebellar atrophy in a dominant Alzheimer's disease family.

We identified the novel PSEN1 pathogenic mutation M84V in 3 patients belonging to a large kindred affected by autosomal dominant Alzheimer's disease (AD). The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging and genetic assessment was performed.

Low Florbetapir PET Uptake and Normal Aβ1-42 Cerebrospinal Fluid in an APP Ala713Thr Mutation Carrier.

According to the literature, the APP Ala713Thr mutation is associated with Alzheimer's disease and cerebral amyloid angiopathy. We describe a case of dementia clinically compatible with frontotemporal dementia in an APP Ala713Thr mutation carrier in which both [18F]Florbetapir PET uptake and Aβ1-42 cerebrospinal fluid levels were normal. Further evidences are required to establish if this association is only incidental.

Analyses of the role of the glucocorticoid receptor gene polymorphism (rs41423247) as a potential moderator in the association between childhood overweight, psychopathology, and clinical outcomes in Eating Disorders patients: A 6 years follow up study.

Childhood overweight and the SNP rs41423247 of the glucocorticoid receptor gene (GR) were reported to represent predisposing factors for Eating Disorders (EDs). The distribution of the polymorphism was evaluated in 202 EDs patients, and in 116 healthy subjects. The Structured Clinical Interview for the DSM-IV and self-reported questionnaires were administered at the admission to the clinic and at 3 time points (end of a cognitive behavioral therapy, 3 and 6 years follow up).

Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late-onset Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease affecting over 20 million people worldwide, mainly adult subjects in advanced age. Over 240 different fully penetrant autosomal dominant mutations in 532 families around the world have been described in three genes [i.e.

Mutation analysis of patients with neurodegenerative disorders using NeuroX array.

Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (NeuroX; Illumina, Inc) tailored to study neurodegenerative diseases (e.

Epigenetic modifications in Alzheimer's disease: cause or effect?

Alzheimer's disease (AD) is a multifactorial disorder induced by a combination of genetic and environmental factors, and epigenetic modifications could be the key to understand the pathogenesis of AD. We performed a methylation study of the promoter regions of the three AD principal causative genes in 60 late-onset AD patients and 60 controls. The studied regions in the three causative genes were strongly unmethylated in both groups, but in AD patients the methylation resulted significantly increased.

Association of the variant Cys139Arg at GRN gene to the clinical spectrum of frontotemporal lobar degeneration.

Background: Progranulin protein (PGRN) is a cysteine-rich growth factor encoded by the progranulin gene (GRN). PGRN mutations were identified in patients with frontotemporal lobar degeneration (FTLD) and recently its role as risk factor has been described in patients with probable Alzheimer's disease (AD). To date, more than 100 genetic variants in GRN gene have been described and the pathogenic nature is still unclear for almost 36% of them.

Imaging and cognitive reserve studies predict dementia in presymptomatic Alzheimer's disease subjects.

There is strong evidence that Alzheimer's disease (AD) pathology starts decades before clinical onset. Cognitive reserve (CR) and brain reserve can be a good predictive model for AD development. Neuroimaging can help in describing cerebral reserves, as well as in detecting AD brain pathology before the onset of clinical dementia.

TOMM40 polymorphisms in Italian Alzheimer's disease and frontotemporal dementia patients.

Chromosome 19 is one of the several prominent chromosomes related to the risk of developing late-onset Alzheimer's disease (LOAD) and frontotemporal lobar degeneration (FTLD). However, only Apolipoprotein E (APOE) has been confirmed as a risk factor for both disorders. The aim of this study was to investigate a set of polymorphisms in the translocase of the outer mitochondrial membrane 40 (TOMM40) gene, located in close proximity to APOE, to clarify if the TOMM40 gene may be considered a risk factor for AD and FTLD, independently of APOE status.

Ataxia-telangiectasia mutated (ATM) genetic variant in Italian centenarians.

Lifespan is attributable to genetic factors and some studies have attempted to identify putative genes implicated in human longevity. Several genetic loci have been associated with longevity, but some of these are not replicable, probably due to the vast differences among ethnicities. We analyzed in 128 Italian long-lived individuals and 150 unrelated healthy subjects, the recently reported association between rs189037 in the ataxia-telangiectasia mutated gene promoter and longevity in Chinese nonagenarians/centenarians.

DAPK1 is associated with FTD and not with Alzheimer's disease.

Apoptosis is correlated with various forms of dementia. Death-associated protein kinase 1 (DAPK1) plays an important role in neuronal apoptosis and could influence the pathology of late-onset Alzheimer's disease (LOAD) and frontotemporal dementia (FTD). It has been reported that two common polymorphisms (rs4878104 and rs4877365) are associated with LOAD, thus we examined the genotype and allele distributions of the above polymorphisms in 681 Italian subjects, including patients with LOAD and FTD.

Suitability of neuropsychological tests in patients with vascular dementia (VaD).

The concept of vascular dementia (VaD) has evolved with the introduction of vascular cognitive impairment (VCI). VaD patients show predominantly frontal cognitive deficits. The executive area is particularly affected, while memory deficits are less frequent in patients with VaD than patients with AD.

Progranulin genetic screening in frontotemporal lobar degeneration patients from central Italy.

Recently, mutations in the progranulin gene (GRN) were reported to account for the vast majority of Frontotemporal lobar Degeneration (FTLD) and a growing number of reports describe the implication of this gene in the development of the FTLD pathology with a significant variation in clinical features. To better clarify the contribution of GRN mutations to Italian FTLD, we screened 381 subjects: 171 cases and 210 healthy subjects, all from Central Italy, particularly of Tuscan origins. GRN gene was analyzed using High Resolution Melting Analysis and automated Genetic Analyzer.

Association Study of Genetic Variants in CDKN2A/CDKN2B Genes/Loci with Late-Onset Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia clinically characterized by progressive impairment of memory and other cognitive functions. Many genetic researches in AD identified one common genetic variant (ε4) in Apolipoprotein E (APOE) gene as a risk factor for the disease. Two independent genome-wide studies demonstrated a new locus on chromosome 9p21.

Implication of a genetic variant at PICALM in Alzheimer’s disease patients and centenarians.

A common polymorphism (rs3851179) in the PICALM (phosphatidylinositol-binding clathrin assembly protein) gene has been recently associated with reduced risk of developing late-onset Alzheimer’s disease (LOAD). We analyzed the genotype and allele distributions of the PICALM polymorphism in 813 Italian subjects, including LOAD patients and centenarians. The segregation of the PICALM rs3851179 showed no statistically significant difference between LOAD cases and controls.

Implication of serotonin-transporter (5-HTT) gene polymorphism in subjective memory complaints and mild cognitive impairment (MCI).

Serotonin-transporter-linked polymorphism (5-HTTLPR) is involved in neuropsychiatric diseases and recently the S-isoform has been correlated with a higher risk of developing emotion-induced retrograde amnesia. In order to better clarify the possible role of the 5-HTT S/L polymorphism and its effects on cognitive ability, especially on memory skills, we report here the distributions of the 5-HTT genetic variant and the Apolipoprotein E (ApoE) ɛ-4 allele and their association with neuropsychological measures in older adults reporting problems with everyday memory. Moreover, we verified the presence of a possible association between the S-allele with depression and the personal trait of neuroticism.

Semantic dementia associated with mutation V363I in the tau gene.

A 46-year-old woman who presented with prosopagnosia was clinically evaluated. Results of neuropsychological measures showed severe impairment in oral naming with anomia and a marked deficit in naming and recognition of famous faces. The clinical diagnosis was semantic dementia (SD).

Fibroblasts from PS1 mutated pre-symptomatic subjects and Alzheimer's disease patients share a unique protein levels profile.

In Alzheimer's disease (AD), a major goal is to improve early detection, as the diagnosis cannot be made until patients exhibit a noticeable decline in cognition and the brain is irreversibly damaged. With this aim in mind, we performed proteome analysis of familial AD fibroblasts from both demented and pre-symptomatic subjects, using a 2D-PAGE based approach and then identifying proteins by mass spectrometry. We compared primary fibroblast cultures from skin biopsy of presenilin 1 (PS1) mutated patients, pre-symptomatic subjects carrying mutations in the PS1 gene but healthy at the time of skin biopsy, and age-matched individuals as control.

Glucocorticoid receptor gene polymorphisms in Italian patients with eating disorders and obesity.

Objective: Glucocorticoids (GCs) are involved in the control of eating behaviors, and it has been proposed that GCs and their receptors (GR) could play a significant role in the pathophysiology of eating disorders (EDs) and obesity. We studied whether genetic variants, such as N363S (rs56149945), exon 9-β (rs6198), ER22/23EK (rs6189-6190), and the intronic BclI restriction site (rs41423247) polymorphisms in the GR gene, could be considered as risk factors for the development of EDs and obesity in Italian patients.

Methods: We investigated the distribution of these single nucleotide polymorphisms in 572 Italian patients: 118 patients with anorexia nervosa, 108 patients with bulimia nervosa, 62 patient with binge eating disorder, 177 obese non-binge eating disorder patients, and 107 unrelated, normal, age-matched controls.

Different implication of NEDD9 genetic variant in early and late-onset Alzheimer's disease.

Alzheimer's disease (AD) is a complex and multifactorial progressive neurodegenerative disease. Recently, two studies reported inconsistent results on a possible involvement of the NEDD9 (neural precursor cell expressed, developmentally down-regulated 9, 6p25-p24) as a candidate gene for the risk of developing AD and/or Parkinson's disease (PD). We analyzed the distribution of the rs760678 SNP polymorphism in 735 Italian subjects: 214 unrelated sporadic late-onset AD patients (LOAD, 64.

Lack of implication for CALHM1 P86L common variation in Italian patients with early and late onset Alzheimer's disease.

A recent study identified a polymorphism (Pro86Leu) in the Calcium homeostasis modulator 1 (CALHM1) gene whose minor Leucine allele showed a higher frequency in Alzheimer's disease (AD) patients compared to controls (29% in AD and 22% in controls). Further studies provided conflicting results in different ethnic groups. In order to assess the involvement of the CALHM1 genetic variant on the risk of developing AD, we analyzed the genotype and allele distributions of the Pro86Leu polymorphism in 758 Italian subjects.

Implication of sex and SORL1 variants in italian patients with Alzheimer disease.

Objective: To investigate the association of genetic variants in sortilin-related receptor (SORL1), which has been proposed as an important genetic contributor to late-onset Alzheimer disease (LOAD).

Design: We analyzed 13 SORL1 single-nucleotide polymorphisms (SNPs) and the relative haplotypes in a case-control association study.

Participants: The sample included 708 Italian subjects: 251 unrelated, sporadic patients with LOAD, 99 sporadic patients with early-onset Alzheimer disease (AD), and 358 healthy controls.