Alzheimer's - Dementia, Author Interviews, Nature / 05.12.2013

Alessandra d’Azzo PhD Department of Genetics, St Jude Children’s Research Hospital 262 Danny Thomas Place, Memphis, Tennessee 38105MedicalResearch.com Interview with: Alessandra d’Azzo PhD Department of Genetics, St Jude Children’s Research Hospital 262 Danny Thomas Place, Memphis, Tennessee 38105 MedicalResearch.com: What are the main findings of the study? Dr. d’Azzo: We have discovered a connection between a rare childhood disorder and Alzheimer’s disease that usually affects older people. The culprit is a metabolic enzyme called NEU1 that normally controls the recycling or disposal of proteins in a specific cell compartment, the lysosome. When NEU1 is defective, children develop the severe metabolic disease, sialidosis. Our study suggests that NEU1 also plays an important role in the development of Alzheimer’s disease. Based on this discovery, we decided to increase NEU1 enzyme activity in the brain of an Alzheimer’s disease mouse model that shows features characteristic of the human disease, namely the accumulation of toxic protein aggregates or plaques. Remarkably, we could significantly diminish the number of plaques in the brain of these mice by increasing NEU1 enzyme activity.
Alzheimer's - Dementia, Author Interviews / 24.10.2013

MedicalResearch.com Interview with: Andrew S. Lim MD MMSc FRCPC DABPN Assistant Professor and Clinician Scientist Division of Neurology, Department of Medicine Sunnybrook Health Sciences Centre University of Toronto MedicalResearch.com: What are the main findings of the study? Dr. Lim: Alzheimer disease (AD) is the result of a confluence of genetic, behavioral, and environmental risk factors.  The Apolipoprotein E (APOE) e4 allele is the most common and well established genetic risk factor for Alzheimer Disease.  10-20% of the US population carries the high risk APOE e4 allele, which confers up to a 30% lifetime risk of AD. Meanwhile, previous work had suggested that poor sleep may be a risk factor for AD and that APOE genotype and poor sleep may amplify each other's negative cognitive effects. We asked the question whether good sleep consolidation (i.e. sound sleep without repeated awakenings) may reduce the effect of APOE on the risk of incident AD and the burden of AD pathology.  We studied 698 individuals without dementia participating in the Rush Memory and Aging Project - a longitudinal cohort study of aging and risk factors for AD.  We measured sleep consolidation using wrist-watch like devices called actigraphs, and followed participants for up to 6 years, examining them annually for the development of AD.  Autopsies were perfumed on 201 participants who died during the follow-up period and we quantified the burden of AD pathology. During the follow-up period, 98 participants developed AD.  As expected, carrying the APOE e4 allele was associated with a higher risk of AD, faster cognitive decline, and a higher burden of AD pathology (amyloid plaques and neurofibrillary tangles) at death. However, better sleep at baseline significantly reduced the negative impact of APOE e4 on the risk of AD, rate of cognitive decline, and burden of neurofibrillary tangle pathology.
Alzheimer's - Dementia, Author Interviews / 03.10.2013

MedicalResearch.com Interview with: Keiichi Yamamoto, MD, PhD Department of Geriatric Medicine and Neurology, Osaka City University Graduate School of Medicine Osaka, Japan. MedicalResearch.com: What are the main findings of the study? Answer: Aβ is normally bound to and transported by albumin in blood. We therefore hypothesized that decreased blood levels of Albumin-Aβ complexes may be associated with decreased Aβ removal from brain to blood, resulting in Aβ accumulation in the brain. This is the first study demonstrated that decreased serum level of albumin-Aβ complexes was strongly associated with a higher prevalence of Alzheimer’s disease (AD). This association was independent of age, sex, and ApoE4 allele. In addition, decreased serum level of albumin-Aβ complexes was correlated with decreased levels of Aβ42 in the CSF and increased levels of p-tau in the CSF, findings that have been shown to be associated with specific neuropathologic findings and AD progression.
Alzheimer's - Dementia, Author Interviews, Genetic Research, Nature / 16.08.2013

MedicalResearch.com Interview with: Steve Estus PhD Dept. of Physiology University of Kentucky Office: Room 332 Sanders-Brown Building 800 S. Limestone Street Lexington, KY 40536-0230 MedicalResearch.com: What are the main findings of the study? Answer: We report evidence for the function of a Alzheimer's genetic  risk factor.  This protective allele of the polymorphism decreases the splicing efficiency of exon 2 in CD33, a receptor protein that regulates microglial activation.  Loss of exon 2 appears to produce a dormant CD33 protein, resulting in increased microglial phagocytosis activity.  Overall, these findings confirm and extend recent papers in Neuron and Nature Neuroscience  (discussed further in our report) that described decreased CD33 activity with the protective SNP allele.
Author Interviews, Mental Health Research, Nature / 12.04.2013

MedicalResearch.com eInterview: Professor Nigel S. Scrutton ScD FRSC FSB Director Manchester Institute of Biotechnology EPSRC Established Career Fellow |Faculty of Life Sciences | Manchester Institute of Biotechnology | University of Manchester | Manchester | M1 7DN | UK | MedicalResearch.com: What are the main findings of your study? Dr. Scrutton: A major breakthrough has been made by our team of researchers seeking treatments for degenerative illnesses such as Parkinson's Disease. We have detailed how an enzyme in the brain interacts with a drug-like lead compound directed against Huntington's Disease (but also with major implications for Alzheimer’s and Parkinson’s diseases) to inhibit its activity. The work – which solved the molecular structure of a crucial brain enzyme called kynurenine 3-monooxygenase – opens the door to effective treatment for neurodegenerative diseases such as Huntington's, Alzheimer's and Parkinson's. The main findings not only describe the molecular details of the enzyme, but also how it interacts with a lead drug compound that inhibits the natural activity of the enzyme.