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The study of neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD), in isolated populations represents a privileged point of view for identifying new causative genes and pathogenetic mechanisms. Vallecamonica is a valley located in the Brescia province (Northern Italy), which experienced isolation until the end of World War II. The aims of the present work were (1) to estimate the prevalence of FTLD in Vallecamonica, (2) to determine the monogenic FTLD forms, and (3) to identify FTLD cases with no evidence of known pathogenetic mutations and the related clinical features. Patients meeting current clinical criteria for FTLD were considered. Mutation analysis for microtubule associated protein tau (MAPT) and progranulin (PGRN) genes was performed, as well as serum PGRN dosage. On the census day, 42 FTLD patients were alive, resulting in an overall disease prevalence of 35 per 100 inhabitants. Thirty-one out of 42 patients underwent sequencing analysis. Five patients carried PGRN Thr272fs mutation and one patient MAPT P301L mutation. There were no differences in term of age at onset and gender between this group and mutation carriers, but the latter had greater family history for dementia (100%, P = 0.01). In Vallecamonica, we detected a higher prevalence of FTLD compared with that already reported in other populations. A founder effect or a genetic drift might be considered for an allelic enrichment. Ongoing study aims to identify the presence of a new genetic form in those FTLD patients without known pathogenetic mutations in this isolated population.

A few epidemiologic studies are available on the prevalence of early-onset Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). The aim of this study was to establish in an Italian population, namely in Brescia County, the prevalence of early-onset neurodegenerative dementia, and how it is shared between AD and FTLD. A network among the participating centers has been established for 10 years. A standardized form was sent to be filled in for each patient. The census day was chosen as December 1, 2009. The prevalence of disease was calculated stratifying patients according to sex and diagnosis. On the census day, 175 patients in the whole population aged 45--65 years were enrolled into the study. The resulting overall prevalence of early-onset neurodegenerative dementia was found of 55.1 per 100,000 inhabitants (95%confidence interval, 47.0--63.4). A comparable prevalence between AD and FTLD was reported (25.5 and 29.6 per 100,000 inhabitants, respectively), and no differences in sex distribution were found both in AD and FTLD. The improvement of knowledge on early-onset neurodegenerative dementias allows us to reconsider its epidemiology and to rethink its impact on public polices. This would be crucial for defining the urgency of treatment approaches.

Frontotemporal Lobar Degeneration (FTLD) is a genetically and pathologically heterogeneous disorder characterized by behavioral change, executive dysfunction and language impairment associated with frontal and temporal lobe degeneration. Three major clinical subtypes have been identified so far, namely behaviour variant Frontotemporal dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia (PNFA). FTLD might also overlap with atypical parkinsonisms or motor neuron disease. Several pathogenetic mutations have been associated with specific pathological and clinical correlates. FTLD associated with either Microtuble Associated Protein Tau (MAPT) or Progranulin (PGRN) mutations is recognised as the most common form of autosomal dominant inherited disorder. However, monogenic mutations account for only about one third of all FTLD cases. Several studies have evaluated the contribution of genetic background in non-monogenic forms of FTLD, with the attempt to establish its role in increasing disease risk and in modulating clinical phenotypes. Specific MAPT and PGRN polymorphisms have been demonstrated to affect disease onset, clinical features and prognosis of FTLD, and genetic variations within other genes appear to play a role in influencing disease risk and clinical expression of FTLD. The aim of the present review is to discuss the impact and the role of genetic background in non-monogenic forms of FTLD, to highlight new potential pathogenetic and therapeutic targets.

Frontotemporal Lobar Degeneration (FTLD) has always been considered a rare disorder, but only a few epidemiologic studies are available. The aim of the present work was to ascertain all FTLD patients in a Northern Italy area from January 2001 to December 2008, and to estimate the disease prevalence. On the census day, 213 FTD patients were still alive, resulting in an overall prevalence of 17.6 per 100,000 inhabitants. The prevalence of FTLD in patients aged 45-65 years was 22 per 100,000 inhabitants (95% CI=17-27). The prevalence of FTLD was the highest in patients aged 66-75 (78 per 100,000 inhabitants, 95% CI=56-100), and it was still high over 75 years (54 per 100,000 inhabitants, 95% CI=36-69). FTLD is a more common form of dementia than previously recognized. Our results claimed that FTLD is not only an early-onset disorder, but it is frequent in advanced age as well.