The Neurobiology of Aging and Alzheimer Disease in Down Syndrome

1st Edition - August 27, 2021
Editors: Elizabeth Head, Ira Lott
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 8 8 4 5 - 3
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 8 8 4 6 - 0

The Neurobiology of Aging and Alzheimer Disease in Down Syndrome provides a multidisciplinary approach to the understanding of aging and Alzheimer disease in Down syndrome that i… Read more

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The Neurobiology of Aging and Alzheimer Disease in Down Syndrome provides a multidisciplinary approach to the understanding of aging and Alzheimer disease in Down syndrome that is synergistic and focused on efforts to understand the neurobiology as it pertains to interventions that will slow or prevent disease. The book provides detailed knowledge of key molecular aspects of aging and neurodegeneration in Down Syndrome by bringing together different models of the diseases and highlighting multiple techniques. Additionally, it includes case studies and coverage of neuroimaging, neuropathological and biomarker changes associated with these cohorts. This is a must-have resource for researchers who work with or study aging and Alzheimer disease either in the general population or in people with Down syndrome, for academic and general physicians who interact with sporadic dementia patients and need more information about Down syndrome, and for new investigators to the aging and Alzheimer/Down syndrome arena.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Acknowledgments
Chapter 1: Introduction
Abstract
History
Prevalence of DS and phenotype
People with DS are living longer
The link between Alzheimer's disease and Down syndrome
Overview of the chapters
Chapter 2: Alzheimer's neuropathology in Down syndrome: From gestation to old age
Abstract
Acknowledgments
Introduction
Prenatal brain pathology in DS
Adult brain pathology in DS
Cortical amyloid in AD and DS
Cerebellar amyloid in AD and DS
Striatal amyloid pathology in AD and DS
Tau deposition in AD and DS
Fetal tau in DS
Tau pathology in the adult AD and DS brain
Evolution of tau pathology in AD and DS
Other pathologies in AD and DS
α-Synuclein inclusions in DS
Cholinergic basal forebrain dysfunction in DS and AD
Prenatal cholinergic basal forebrain connectome in DS
Adult cholinergic basal forebrain connectome in AD and DS
Endosomal dysfunction in AD and AD
Synaptic integrity in AD and DS
Gene expression profiling in DS
Single cell expression profiling in DS
Summary
Chapter 3: The contribution of inflammation to Alzheimer's disease in Down syndrome
Abstract
Introduction
Neuroinflammation in Alzheimer's disease
Neuroinflammation in Down syndrome—Genetics
Neuroinflammation in Down syndrome: Biomarker studies
Neuroinflammation as a function of age and AD: Autopsy studies
Drug development for AD with a focus on neuroinflammation
Conclusions
Chapter 4: The role of cerebrovascular disease in aging and Alzheimer's disease among people with Down syndrome
Abstract
Acknowledgments
Introduction
Cerebrovascular pathology
Neuroimaging-derived markers of cerebrovascular disease in adults with Down syndrome
Summary
Chapter 5: Oxidative stress and mTOR in Down syndrome brain: Link to Alzheimer's dysmetabolism, neuropathology, and possible therapies
Abstract
Genetics of oxidative stress in Down syndrome
Primer of the mTOR pathway
mTOR as a link between Aβ and tau pathology
Potential interventions
Summary
Chapter 6: Fluid biomarkers for Alzheimer's disease in Down syndrome: Current status and novel trends
Abstract
Acknowledgments
Introduction
Plasma and CSF biomarkers in Down syndrome
Beyond amyloid, Tau, and NfL: New emerging biomarkers
Concluding remarks
Chapter 7: Proteomic and metabolomic biomarkers of Alzheimer's disease: Opportunities to advance precision medicine and clinical trials
Abstract
Acknowledgments
Proteomic and metabolomic methodologies
Proteomic profiles and predictors of dementia
Metabolomics: A practical primer
Down syndrome-Alzheimer’s disease: A metabolic dementia?
Proteomic and metabolomic biomarkers for precision medicine and outcomes for clinical trials
Conclusion
Chapter 8: Magnetic resonance imaging biomarkers for cognitive decline in Down syndrome
Abstract
Acknowledgments
Introduction
Structural neuroimaging
Diffusion-based neuroimaging
Resting state functional neuroimaging
Arterial spin labeling
Magnetic resonance spectroscopy
Summary
Chapter 9: PET imaging in Down syndrome and Alzheimer's disease
Abstract
Introduction
Utility of pet imaging for studying ad pathology
FDG PET
Amyloid PET
TAU PET
Summary
Summary
Chapter 10: Genetics of Alzheimer's disease in adults with Down syndrome
Abstract
Acknowledgments
Alzheimer's disease in adults with Down syndrome
Advantages of studying the genetics of Alzheimer's disease in Down syndrome
Other high-risk populations: Autosomal dominant Alzheimer's disease (ADAD)
Genes on chromosome 21
Genes outside chromosome 21 with a reported association with dementia in adults with DS
Recently identified genes associated with AD in the general population
Future directions
Chapter 11: Co-occurring medical conditions in aging adults with Down syndrome
Abstract
Prevalence
Longevity and survival
Aging
Medical comorbidities in adults
Hospitalizations
Medical comorbidities in elderly adults (> 40 years) (see also Chapter 13)
Mental Health
Sleep apnea
Audiologic concerns
Ophthalmologic
Thyroid
Cardiovascular
Menopause
Bone metabolism
Spine
Seizures
Extrapyramidal symptoms
Feeding-swallowing
Conclusion
Chapter 12: Sleep in aging adults with Down syndrome and its association with Alzheimer's disease
Abstract
Obstructive sleep apnea in adults with DS
Future research directions
Other sleep disturbances
Sleep and Alzheimer's disease in Down syndrome
Summary
Chapter 13: Contributions of the neurological examination to the diagnosis of dementia in Down syndrome
Abstract
Acknowledgments
The neurological history
Elements on the general physical examination of neurological interest in DS
The neurological examination
Conclusions
Chapter 14: Psychiatric issues in aging and dementia
Abstract
Acknowledgments
Epidemiology
DS and depression
DS disintegrative disorder
Diagnosis
Treatment approaches
Chapter 15: Cognitive profile of aging and dementia
Abstract
Acknowledgments
Demographic patterns and consequences of longevity
The cognitive and behavioral phenotype of DS
Age-related changes in cognitive functioning
Alzheimer's disease (AD) and its clinical progression in neurotypical adults
Cognitive decline with AD in adults with DS
The relation between cognitive functioning and biomarkers in individuals with DS
Discussion and future directions
Chapter 16: Clinical trials for Alzheimer's disease in Down syndrome
Abstract
Clinical trials—An overview
Clinical trials for Alzheimer's disease in Down syndrome
Amyloid as a drug target
Dyrk1A as a drug target
The Alzheimer's Biomarker Consortium for Down syndrome
Treatment trials in DS
Vitamin E
Memantine
Scyllo-inositol
ACI-24
Horizon21
The Alzheimer's Clinical Trial Consortium for Down syndrome
Conclusions
Chapter 17: Future directions
Abstract
Index

Elizabeth Head

Dr. Head received a Masters in Psychology and a Ph.D. in Neuroscience from the University of Toronto, Canada. She received postdoctoral training at the Institute for Brain Aging & Dementia at the University of California – Irvine. Dr. Head moved to the University of Kentucky in January of 2009 and was a Professor and Associate Director of Education at the Sanders-Brown Center on Aging. In 2019, she returned to the University of California at Irvine, where she is a Professor and Vice Chair for Research in the Department of Pathology & Laboratory Medicine. Dr. Head has dedicated over 20 years to the study of aging and Alzheimer’s disease with a focus on people with Down syndrome. The goal of her research is to help develop interventions that will promote healthy aging in people with Down syndrome.

Affiliations and expertise

Professor and Vice Chair for Research, Department of Pathology & Laboratory Medicine, University of California, Irvine, CA, United States

Ira Lott

Dr. Lott is an Emeritus Professor of Pediatrics and Neurology at the University of California, Irvine. His training was at the Massachusetts General Hospital, Harvard Medical School and he was appointed as the first Clinical Director of the Eunice Kennedy Shriver Center for people with intellectual disability. Since his recruitment to UCI in 1983, he has served as Division chief in pediatric neurology, Chair of Pediatrics and Associate Dean for Clinical Neuroscience. Dr. Lott’s research on development and aging in people with Down syndrome has been continuously funded by the National Institutes of Health for over 25 years. He has received award recognition for his work at the international, national and state levels. Having trained generations of medical students and resident physicians, Dr. Lott’s approach focuses on the intersection between neuroscience and clinical practice.

Affiliations and expertise

Founding Director, Down Syndrome Program, University of California, Irvine, CA, USA

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