Neurotez (United States)

Adipocyte-derived leptin is a pleiotropic hormone implicated in control of lipid storage and mobilization, bone homeostasis, immune function and neuronal plasticity. Leptin has been shown to prevent accumulation of extracellular Aβ and hyperphosphorylation of tau in both cell culture and animal models. Herein an investigation was undertaken to test leptin’s ability to prevent the exacerbation/activation of AD-related pathways in neurons following their exposure to a high concentration of a variety of lipids. Specifically, cholesterol, oleic acid and/or ceramide were added to the media of cells resulting in decreased cellular viability and energy metabolism, and in increased tau phosphorylation and extracellular Aβ. Leptin increased viability, boosted cellular metabolism by activating AMP-activated protein kinase (AMPK) and the sirtuins (SIRT) and reduced tau phosphorylation and Aβ accumulation in a dose-dependent manner in response to select challenges. These findings demonstrate that leptin can attenuate the harmful effect of certain lipids that lead to exacerbation or activation of AD pathways. The study herein also provides the basis for a novel screening platform to define and identify a novel class of “metabolic” compounds addressing Alzheimer’s disease, based on a biological profile similar to leptin.

Recent studies have shown that the translocase of outer mitochondrial membrane 40 homolog (TOMM40) contains a polymorphic poly-T variant, the long variant of which is associated with an increase in AD incidence among APOE 3 carriers. Current methods to isotype the poly-T region rely on long PCR, subcloning and sequencing to distinguish among the allelic variants. While such methods are extremely accurate as well as quantitative in determining the number of T residues in the poly-T region, the process can be cumbersome, time consuming and expensive to employ in routine laboratories. To this end, we have developed a quick and simple method to isotype the human TOMM40 variable length polymorphism using a PCR- and restriction digest-based approach, enabling rapid genotyping of TOMM40 variants.

The objective of this study was to assess in patients with HIV perceptions of life pre-HIV versus post-HIV diagnosis and examine whether such perceptions change over time. We conducted interviews and chart reviews of 347 outpatients with HIV from three cities in 2002-2004. In two interviews 12-18 months apart, patients compared their life now with their life before HIV was diagnosed. Independent variables included demographic and clinical characteristics; HIV-specific health status, symptoms, and concerns; spirituality/religion; social support; self-perception; and optimism. The patients' mean (standard deviation [SD]) age was 44.8 (8.3) years; half were minorities; and 269 (78%) were taking antiretroviral therapy. Comparing life at time 1 versus before diagnosis, 109 (31%) patients said their life was better at time 1, 98 (28%) said it was worse, and the rest said it was about the same or did not know. By time 2, approximately one fifth of the patients changed their answers to indicate life improvement and one sixth changed them to indicate life deterioration. In multivariable analysis, change in perception for the better between time 1 and time 2 (versus prediagnosis) was positively associated with time 1 positive religious coping scores, whereas change in perception for the worse was associated with study site, heterosexual orientation, a detectable viral load, shorter duration of HIV, lower spirituality scores, and lower positive religious coping scores. We conclude that many patients with HIV feel that their life is better than it was before their diagnosis, although results of such comparisons often change over time.