Researchers Present Alzheimer’s and Autism Breakthroughs

Newswise — At The Society for Neuroscience annual meeting, Dr. Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Geriatrics and Adult Development and Director of the Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer's disease at Mount Sinai School of Medicine in New York presented the following new breakthrough research findings for Alzheimer's disease and other brain disorders.

Grape Seed Extract Prevents Alzheimer's Disease A recent study in Dr. Pasinetti's laboratory at Mount Sinai explored a commercially-available Meganatural AZ grape seed extract as a novel alternative to moderate red wine consumption to prevent Alzheimer's disease. Dr. Pasinetti showed that the naturally derived Meganatural AZ grape seed extract is an effective agent for the prevention of Alzheimer's disease memory loss and brain degeneration in a mouse model of Alzheimer's disease.

Dr. Pasinetti's research on the Meganatural AZ grape seed extract is part of a growing push to identify and develop more effective natural treatments for Alzheimer's disease. Meganatural AZ revealed to be an effective agent in reducing β-amyloid in brain cells. Since abnormally processed beta-amyloid has been identified as playing a key role in Alzheimer's disease pathogenesis, particularly in respect to cognitive deterioration, Dr. Pasinetti's discovery suggests that Meganatural AZ may be a useful currently available agent to prevent or treat Alzheimer's disease memory loss by reducing beta-amyloid in the brain.

Daily Moderate Consumptions of a Red Muscadine Wine Prevents Cognitive DeclineResearchers at Mount Sinai continue to explore whether other red wines might provide similar benefits in AD prevention and/or therapy. In the present study using the Tg2576 mouse AD model, they assessed the potential benefit of long-term, daily moderate consumptions of the red wine, Muscadine (Vitis rotundifolia), in AD prevention. Dr. Pasinetti confirmed that under this treatment paradigm, the daily Muscadine intake by Tg2576 mice is equivalent to moderate daily wine consumption of one 5-ounze drink per women and two drinks for men. Similar to their observation with Cabernet Sauvignon, they found that moderate Muscadine wine consumption significantly attenuated age-dependent development of Aβ neuropathology and cognitive dysfunction in Tg2576 mice. Their evidence suggested that the polyphenol components in Muscadine wine are the bioactive components responsible for attenuating cognitive impairment in Tg2576 mice, in part, by interfering with the formation of high molecular weight (HMW) Aβ-oligomers, which are directly implicated in cognitive dysfunction. Mount Sinai's studies strengthen the hypothesis that moderate red wine consumption may delay (or prevent) AD onset. Moreover, these studies highlight a promising new mechanism by which polyphenolic compounds from red wine, and perhaps from other dietary sources might be developed as AD preventive and/or therapeutic measures.

NIC5-15 a Natural Pine-Cones Derived Compound with Anti-Diabetic Properties Prevents Alzheimer' Disease - Type Cognitive DeteriorationRecent epidemiological and experimental evidence suggest that attenuation or prevention of diabetic conditions may reduce the incidence of Alzheimer's disease. Consistent with this evidence, studies in Dr. Pasinetti's laboratory suggest that insulin "re-sensitization" in experimental mouse models of Alzheimer's disease may slow down the onset and eventually the progression of Alzheimer' disease. Recent evidence in Mount Sinai's lab suggests that NIC-15, a traditional insulin sensitizer herbal agent that occurs in pine tree components (among other plants or vegetables), can mitigate Alzheimer's disease type neuropathology in transgenic models of Alzheimer's disease cognitive deterioration. Based on this observation, Dr. Pasinetti laboratory, decided to continue to explore the mechanisms through which treatment of diabetic AD-mice with NIC5-15 in mouse models may beneficially attenuates Alzheimer's disease type neuropathology.

They report that 5-months old diabetic Tg2576 mice treated for 6 months with NIC5-15 by incorporation of the drug into the drinking water significantly attenuated Alzheimer's disease type cognitive deterioration coincidental with attenuation diabetic conditions. Most interestingly they found that NIC5-15 improved cognitive performance in insulin-resistant mice that develop AD-type neuropathology through mechanism involving inhibition of Alzheimer's disease type amyloid neuropathology. The lab also found that a mechanisms through which NIC5-15 may attenuate Alzheimer's disease type conditions is through the inhibitions of an enzyme also known as γ-secretase, which is involved in abnormal generation of amyloid in the brain of Alzheimer's disease cases. Thus, characterization of NIC5-15 preventing abnormal β-amyloid generation will help in the identification of future, novel disease modifying - pharmacological treatments for Alzheimer's disease. Dr. Pasinetti's group also found that the inhibition of the γ-secretase NIC-15 was highly safe and rather selective in influencing only β-amyloid, since y-secretase activity may in same cases also influence the activity of certain protective proteins also known as "Notch" which are protein necessary for brain cell survival. These Mount Sinai studies suggest that NIC5-15, a traditional anti-diabetic herbal agent that occurs in pine tree components (among other plants or vegetables), can mitigate AD cognitive deterioration. Based on this exciting evidence Dr. Pasinetti is currently assessing the effects of NIC5-15 in patients with mild to moderately severe Alzheimer's disease dementia.

Personalized Medicine in Autistic Spectrum Disorder Autism spectrum disorders often remain unrecognized and undiagnosed until, or after late preschool age due to the lack of appropriate and selective screening procedures in young children, particularly among toddlers. Development of clinically accessible molecular signatures may improve disease diagnosis at a young age and promote early-individualized treatment, which may ultimately improve the outcome for autistic children and their families. Using a combination of microRNA (miRNA) and proteomic technology platforms, Dr. Pasinetti's laboratory at Mount Sinai used novel molecular signatures as potential practical and accurate diagnostic assay for Autism spectrum disorders. Dr. Pasinetti reports the identification of two sets of miRNA in circulating peripheral blood monocyte cells (PBMC) which selectively and redundantly target and influence the activity of gene products previously implicated in abnormal brain structural/behavioral abnormalities and mitochondrial activities in high functioning autistic spectrum disorder subjects. The development of clinically accessible molecular signatures such as these identified miRNA may improve disease diagnosis at a young age and promote early-individualized treatment, which may ultimately improve the outcome for autistic children and their families.

Dr. Pasinetti anticipates that his work will lead to earlier interventions and more specific treatments predicated on the individual's specific biochemical fingerprint. This is in stark contrast to current medical practice. Personalized medicine offers the alluring promise and potential of uncovering the largely 'unseen' details in autistic spectrum disorders causality and selective response to drug treatments.