How dopamine tunes parvalbumin interneurons in the hippocampus:new experimental observations in Alzheimer's disease

Despite decades of dedicated resea rch,Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disorder for which the mechanisms of onset are sti unc ear.AD is cha racterized by featured histological alterations including amyloid-beta (AB) plaque deposition,accumulation of neurofibrillary to ngles of hyperphosphorylated-tau,and neuronal loss,accompanied by progressive cognitive decline and behavioral changes.

Calcium handling:a strategy to fight neurodegeneration in Alzheimer's disease

In the last few years,preclinical and clinical studies identified the ventral tegmental area(VTA)as one of the first brain regions to be affected in the prodromal phase of Alzheimer's disease(AD).The VTA is a deep midbrain nucleus rich in dopaminergic neurons that innervates and releases dopamine(DA)in several cortical and subcortical brain regions.DA plays a crucial role in the modulation of both cognitive and noncognitive functions and failure of its release underlies both cognitive and neuropsychiatric symptoms in patients with AD.

Nilotinib:from animal-based studies to clinical investigation in Alzheimer's disease patients

Since their first description in the brains of patients suffering from Alzheimer ’s disease(AD), more than 100 years ago, extracellular amyloid-β(Aβ) plaques and intracellular neurofibrillary tangles have been the principal focus of AD research. However, this focus has led to the failure of several long and promising clinical trials, and the efficacy of new Aβ-targeting drugs to slow down the disease progression is still controversial despite being successful in reducing the Aβ load.

Urinary polyomavirus infections in neurodevelopmental disorders

We have recently reported enhanced frequencies of polyomavirus infection in post-mortem brain tissue of autistic patients compared to controls. To further explore potential contributions to neurodevelopmental disorders by polyomaviruses, we have employed specie-specific TaqMan assays to assess the prevalence and titres of BKV, JCV and SV40 inthe urines of 87 patients with autism spectrum disorder, 84 controls matched by sex and age with the autistic sample, 15 subjects with Down syndrome and 13 fragile X individuals. Prevalence rates of urinary BKV infection were significantly greater in Down syndrome and fragile X patients compared to autistic and control individuals (P < 0.01). In a large majority of patients who showed the presence of urinary genomes, viral titres resulted significantly higher among Down syndrome patients (P < 0.01) compared to controls, autism spectrum disorder and fragile X individuals, who did not significantly differ from each other. Our results are consistent with previous evidence supporting hampered immunological surveillance and/or immune deficits in fragile X and especially in Down syndrome patients.

Autism genetics: Methodological issues and experimental design

Autism is a complex neuropsychiatric disorder of developmental origin, where multiple genetic and environmental factors likely interact resulting in a clinical continuum between "affected" and "unaffected" individuals in the general population. During the last two decades, relevant progress has been made in identifying chromosomal regions and genes in linkage or association with autism, but no single gene has emerged as a major cause of disease in a large number of patients. The purpose of this paper is to discuss specific methodological issues and experimental strategies in autism genetic research, based on fourteen years of experience in patient recruitment and association studies of autism spectrum disorder in Italy.