77 research outputs found
The sea urchin embryo: A model to study Alzheimer’s beta amyloid induced toxicity
Alzheimer’s disease (AD) is the most common form of dementia. The cause of AD is closely related to the
accumulation of amyloid beta peptide in the neuritic plaques. The use of animal model systems represents
a good strategy to elucidate the molecular mechanism behind the development of this pathology.
Here we use the Paracentrotus lividus embryo to identify molecules and pathways that can be involved in
the degenerative process. As a first step, we identified the presence of an antigen related to the human
APP, called PlAPP. This antigen, after gastrula stage, is processed producing a polypeptide of about
10 kDa. By immunohistochemistry we localized the PlAPP antigen in some serotonin expressing cells.
Similarly, after 48 or 96 h incubation, a recombinant b-amyloid peptide, rAb42, accumulates around
the intestinal tube and oesophagus. In addition, incubation of sea urchin embryos with two different
solutions rich in oligomers and fibrillar aggregates of rAb42 induce activation of apoptosis as detected
by TUNEL assay. Moreover, we demonstrate that aggregates induce apoptosis by extrinsic pathway activation,
whereas oligomers induce apoptosis both by extrinsic and intrinsic pathway activation. Utilizing
an apoptotic inhibitor, caspases activation was offset and morphological damage rescued. Taken together
all these observations suggest that the sea urchin may be a simple and suitable model to characterize the
mechanism underlining the cytotoxicity of Ab42
Immunosenescence, inflammation and Alzheimer’s disease
Ageing impacts negatively on the development of the immune system and its ability to fight pathogens. Progressive changes in the T-cell and B-cell systems over the lifespan of individuals have a major impact on the capacity to respond to immune challenges. The cumulative age-associated changes in immune competence are termed immunosenescence that is characterized by changes where adaptive immunity deteriorates, while innate immunity is largely conserved or even upregulated with age. On the other hand, ageing is also characterized by “inflamm-ageing”, a term coined to explain the inflammation commonly present in many age-associated diseases. It is believed that immune inflammatory processes are relevant in Alzheimer’s disease, the most common cause of dementia in older people. In the present paper we review data focusing on changes of some immunoinflammatory parameters observed in patients affected by Alzheimer’s diseas
A novel B cell population revealed by a CD38/CD24 gating strategy: CD38(-)CD24 (-) B cells in centenarian offspring and elderly people
The B cell arm of adaptive immunity undergoes significant modifications with age. Elderly people are characterized by impaired B cell responses reflected in a reduced ability to effectively respond against viruses and bacteria. Alterations of immunity with advancing age (immunosenescence) have been widely studied in centenarians who are considered a good example of successful aging. In recent years, attention has shifted to centenarian offspring (CO) as a model of people genetically advantaged for healthy aging and longevity. Here, we describe the preliminary characterization of a proposed new population of memory B cells, defined as CD19(+)CD38(-)CD24(-), which we find at higher frequencies in the elderly but less so in CO than healthy age-matched random controls. In addition, we found a decreased expression of RP105 (CD180), a toll-like receptor-associated molecule, on these cells. CD180 downregulation may potentially be a marker of immunosenescence. Moreover, we show that these CD19(+)CD38(-)CD24(-) B cells produce TNF and hypothesize that their observed expansion in the elderly might contribute to the increased inflammatory status sometimes designated "inflamm-aging
Immune profiling of Alzheimer patients
Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the diseas
Long-term follow-up of HIV-infected patients in salvage therapy with raltegravir plus optimized background regimens: a multicentre Italian experience
Muscle symptoms and creatine phosphokinase elevations in patients receiving raltegravir in clinical practice: results from a multicenter study
Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?
Background: In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). Methods: To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50–59 and 60–69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years). Results: In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20– 1.52), hypertension (aRR 1.52, 95% CI 1.22–1.89), liver disease (aRR 1.78, 95% CI 1.32–2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65–5.03) and multimorbidity (aRR 1.36, 95% CI 1.21–1.54). These findings were confirmed in strata of age, adjusting for sex. Conclusions: Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age
Simple model systems: a challenge for Alzheimer's disease
The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD), one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds
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