Bursting Neurons and Fading Memories :An Alternative Hypothesis of the Pathogenesis of Alzheimer’s Disease

Publication subTitle :An Alternative Hypothesis of the Pathogenesis of Alzheimer’s Disease

Author: D'Andrea   Michael R.  

Publisher: Elsevier Science‎

Publication year: 2014

E-ISBN: 9780128019887

P-ISBN(Paperback): 9780128019795

P-ISBN(Hardback):  9780128019795

Subject: Q189 Neurobiology;R741 Neurology

Language: ENG

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Description

Advances in Alzheimer’s disease (AD) research have been challenging and without major breakthroughs in understanding its pathological basis. The reigning hypothesis suggests AD is the result of extracellular amyloid deposition that seed to form amyloid plaques, which then grow and kill neighboring neurons. However, there are several inconsistencies with this hypothesis, not to mention the inability to show clinical benefit in several failed clinical trials by pharmaceuticals (i.e., from Pfizer, Eli Lilly, etc.), and it is in the field’s best interest to explore and test multiple hypotheses for pathology rather than drive the majority of research on this single amyloid theory. Reviewing many scientifically peer-reviewed publications, this book describes the "Inside-Out" hypothesis on how amyloid escapes the circulatory system through a dysfunctional blood-brain barrier to bind to the alpha 7 nicotinic acetylcholine receptor on pyramidal neurons. Over time, excessive amounts of amyloid appear to be internalized, resulting in neuron death and lysis. This simple mechanism readily explains plaque composition, size, shape, and location. Based on the current direction of research in the field, this hypothesis appears years from any research and development.

  • The clear, compelling, and unifying "Inside-Out" hypothesis of AD is brought to life through a string of scientific publications, synthesizing many known features of disease pathology
  • A high-level text on AD

Chapter

About the Author

Preface

Acknowledgments

Introduction

References

Chapter 1 - Alzheimer’s Disease Today

Neurological factors

Non-neurological factors

The amyloid cascade

Looking ahead

References

Chapter 2 - Seeds of a New Perspective

Histology

Ready to start

References

Chapter 3 - Introducing the “Inside-Out” Hypothesis

Presentation time

References

Chapter 4 - Addressing Technical Concerns

Lipofuscin

Primary antibodies

Heat is the ticket

Antibodies

In situ ELISA

References

Chapter 5 - The Good Intentions of Formic Acid

Formic acid is the problem

Running like mascara

Reference

Chapter 6 - Connecting MAP-2 and Cell Lysis

Reverse logic

Diffuse plaques are benign

Troublesome end point

Reference

Chapter 7 - Classifying Plaques

Three dimensions

Multiple colors

Inflammation

Triple IHC

Microglia’s unanticipated location

The diffuse amyloid plaque

Diffuse–vascular amyloid plaques

Dense–vascular amyloid plaques and others

Call for a nomenclature

References

Chapter 8 - When Is a Star Like a Plaque?

Similar initial hypotheses

New technology

Reflections of a discovery

Reinforcing evidence

Star nomenclature

Scientific parallels

Composition

Closing comment

References

Chapter 9 - The Inflammation Cascade

References

Chapter 10 - Innocent Ab42

References

Chapter 11 - The Alpha 7 Nicotinic Acetylcholine Receptor

References

Chapter 12 - Immunoglobulin: Another Perpetrator

Immunoglobulin neurons

Degenerating Ig-positive neurons

References

Chapter 13 - Add AD to the List of Autoimmune Diseases

References

Chapter 14 - The BBB and BRB in AD

BRB, a vascular harbinger

In vivo BBB support

References

Chapter 15 - “Inside-Out” in the Field

Neuronal death by amyloid (via vascular issues)

Neuronal death by ApoE4

Neuronal death by inflammation

Neuronal death by tau

Neuronal death by autoantibodies

Miscellaneous notes

References

Chapter 16 - Alzheimer’s Disease Tomorrow

State of the AD nation

Targeting the a7 receptor

Targeting Ab42: not plaques

Targeting the BBB

Targeting inflammation

Biomarker discovery

Assessing BBB integrity via BRB

New work

Closing statement

References

Glossary

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