An excess accumulation of advanced glycation end products (AGEs) has been reported in autism brains. Through their interaction with their putative receptor RAGE, AGEs can promote neuroinflammation, oxidative stress and neuronal degeneration. To shed more light on the possible alterations of the AGEs-RAGE axis in autism, hereto we measured plasma levels of endogenous secretory RAGE (esRAGE) and its proinflammatory ligand S100A9 in 18 young adults with autistic spectrum disorder (ASD) and 18 age- and gender-matched healthy comparison subjects. The Childhood Autism Rating Scale (CARS) was used to assess the severity of autistic symptoms. Significantly reduced levels of esRAGE (P = 0.0023) and elevated concentrations of S100A9 (P = 0.0012) were found in ASD patients as compared to controls. In autistic patients, there was a statistically significant positive correlation between CARS scores and S100A9 levels (r = 0.49, P = 0.035), but no significant correlation was seen between esRAGE and S100A9 values (r = -0.23, P = 0.34). Our results of a significantly reduced peripheral level of esRAGE coupled with elevated S100A9 point to a subtle but definite dysfunction of the AGEs/RAGE axis in autism that could play a role in the pathophysiology of this disorder.

Adult↗

PubMed2006

The M694V variant of the familial Mediterranean fever gene is associated with sporadic early-onset Alzheimer's disease in an Italian population sample.

BACKGROUND: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer's disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. METHODS: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. RESULTS: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24-6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34-1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). CONCLUSION: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population.

Age of Onset↗

PubMed2006

Reduced plasma apelin levels in patients with autistic spectrum disorder.

BACKGROUND: Dysregulation of the vasopressin (AVP) system has been implicated in the pathogenesis of autistic spectrum disorder (ASD). Apelin is a recently discovered neuropeptide that could counteract AVP actions and whose receptors are colocalized with vasopressin in hypothalamic magnocellular neurons. Aims of the present study were to investigate circulating levels of apelin in patients with ASD and to assess their correlation with plasma AVP concentrations. METHODS: Plasma levels of apelin and AVP were measured in a total of 18 patients with ASD and 21 age- and gender-matched healthy comparison subjects. The Childhood Autism Rating Scale (CARS) was used to assess the severity of autistic symptoms. RESULTS: Significantly reduced levels of apelin (p < 0.001) and elevated concentrations of AVP (p = 0.02) were found in ASD patients as compared to controls. Additionally, a significant inverse correlation between apelin and AVP levels was found within the ASD group (r = -0.61; p = 0.007), but not in healthy participants (r = -0.26; p = 0.25). Multivariate linear regression analysis showed that only AVP concentrations independently predicted apelin values in ASD individuals (beta = -0.42, t = 2.63, p = 0.014). No correlation was seen between apelin levels and CARS scores (r = -0.10; p = 0.68). CONCLUSIONS: Our findings of a significantly reduced peripheral level of apelin coupled with elevated AVP point to a subtle but definite vasopressinergic dysfunction in autism that could play a role in the etiopathophysiology of this disorder in humans.

Adolescent↗

PubMed2006