Neuroprotection in Alzheimer's Disease

Illana Gozes

• Publisher: Academic Press
• Year: 2016
• ISBN:
  9780128037126
• Topic: Psychology
• Subtopic: Cognitive Neuroscience & Neuropsychology
• Index: Psychology

Neuroprotection in Alzheimer's Disease offers a translational point-of-view from both basic and clinical standpoints, putting it on the cusp for further clinical development with its emphasis on nerve cell protection, including the accumulation of knowledge from failed clinical trials and new advances in disease management.

This book brings together the latest findings, both basic, and clinical, under the same cover, making it easy for the reader to obtain a complete overview of the state-of-the-field and beyond. Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of dementia cases. It is a progressive brain disease that slowly destroys memory, thinking skills, and eventually, even the ability to carry out the simplest tasks. It is characterized by death of synapses coupled to death nerve cells and brain degeneration which is manifested by loss of cognitive abilities. Understanding neuroprotection in Alzheimer's disease will pave the path to better disease management and novel therapeutics.

• Comprehensive reference detailing neuroprotection in Alzheimer's Disease, with details on nerve cell protection and new advances in disease management
• Combines the knowledge and points-of-view of both medical doctors and basic scientists, putting the subject at the forefront for further clinical development
• Edited by one of the leading researchers in Alzheimer's Disease

Chapter 1

Introduction

I. Gozes    The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, The Elton Laboratory for Molecular Neuroendocrinology; Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine; The Adams Super Center for Brain Studies and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel

Keywords

magnetic resonance spectroscopy

Alzheimer’s disease

amyloid

neuroprotection

creatine

gene

Searching clinicaltrials.gov for “neuroprotection” AND “Alzheimer” yielded seven results with four completed studies, of which, one has results. The study is entitled: “Effects of Memantine on Magnetic Resonance (MR) Spectroscopy in Subjects at Risk for Alzheimer’s Disease” (NCT00933608). Rather than concentrating on amyloid and tau, the study highlights the marked cell damage that precedes the clinical manifestation of Alzheimer’s disease (AD) and suggests that targeting populations at risk with pharmacological interventions is a possible strategy to lessen the burden of the disease.

The study population included cognitively normal individuals with subjective memory complaints with biological characteristics of early AD and family history of AD. The primary outcome of the study was change in N-acetylaspartate (NAA) measured with magnetic resonance spectroscopy (MRS). NAA is a metabolite found predominately in neuronal cells, and its amount indicates tissue well-being (the higher the better). In MRS studies, NAA (and other metabolites like choline) are presented as a ratio to creatine (Cr, internal standard) also measured by MRS. Participants took the drug once daily for 4 months. No significant change was reported. Two other studies are in their initial stages, one with low dose nicotine and one with lithium; importantly, these avenues have been previously explored, but the question is, how early should one begin?

Here, we grouped selected scientists across the globe to give us their point of view of Alzheimer’s neuroprotection, mostly from the preclinical point of view, but touching on clinical trials, each with his/her point of view. Starting from a global overview through animal models and personal prisms of interest, we travel down the path of AD neuroprotection. Gene/proteins associated with the disease are highlighted as potential new avenues for diagnostics and intervention, beyond acetylcholine esterase inhibitors, memantine, and amyloid vaccination. The more we know about the disease, the better potential for intervention, till AD becomes only a memory.

Chapter 2

Neural Regeneration as a Disease-Modifying Therapeutic Strategy for Alzheimer’s Disease

S.F. Kazim^*,**

K. Iqbal^*
* Department of Neurochemistry, & SUNY Downstate/NYSIBR Center for Developmental Neuroscience, New York State Institute for Basic Research (NYSIBR), Staten Island, NY, United States
^** Neural and Behavioral Science Program, School of Graduate Studies, State University of New York (SUNY) Downstate Medical Center, Brooklyn, NY, United States

Abstract

Alzheimer’s disease (AD) is the most common age-dependent neurodegenerative disorder, which contributes significantly to the health care burden particularly in the developed world. As yet, there is no effective treatment for AD. Besides the presence of amyloid β plaques and neurofibrillary tangles, AD is characterized by neurogenic and synaptic failure leading to cognitive decline. Neural regeneration–based strategy represents a highly promising therapeutic approach for AD. Shifting the balance from neurodegeneration to neural regeneration with neurotrophic small-molecule peptide mimetics has shown promise in the animal models of AD. Our work with a ciliary neurotrophic factor–based neurogenic and neurotrophic peptidergic compound has shown that neural regeneration–based therape...

Table of contents

• Cover
• Title page
• Table of Contents
• Copyright
• Dedication
• List of Contributors
• Acknowledgments
• Chapter 1: Introduction
• Chapter 2: Neural Regeneration as a Disease-Modifying Therapeutic Strategy for Alzheimer’s Disease
• Chapter 3: Animal Models of Alzheimer’s Disease
• Chapter 4: Mechanisms of Neuronal Microtubule Loss in Alzheimer’s Disease
• Chapter 5: Tau-Centric Therapies for Treating Alzheimer’s Disease
• Chapter 6: The Potential of Small Molecules in Preventing Tau Oligomer Formation and Toxicity
• Chapter 7: A Novel Neuroprotection Target With Distinct Regulation in Stroke and Alzheimer’s Disease
• Chapter 8: Sirtuin Modulation as Novel Neuroprotective Strategy for Alzheimer’s Disease
• Chapter 9: Rescue of Neurons by Resolving Inflammation
• Chapter 10: Targeting Transition Metals for Neuroprotection in Alzheimer’s Disease
• Chapter 11: Multifunctional Effects of Human Serum Albumin Toward Neuroprotection in Alzheimer Disease
• Chapter 12: RGS2 and SIRT1 Link Renin Angiotensin Aldosterone System to Alzheimer’s Disease
• Chapter 13: Neuroprotective Drug Development: The Story of ADNP, NAP (Davunetide), and SKIP
• Author Index
• Subject Index