Amyloid and tau in the brain in sporadic Alzheimer’s disease: defining the chicken and the egg

Cheryl A Hawkes,Roxana O Carare,Roy O Weller

doi:10.1007/s00401-014-1243-9

Cheryl A Hawkes, Roxana O Carare + Show 1 more

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https://doi.org/10.1007/s00401-014-1243-9

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Journal: Acta Neuropathologica	Publication Date: Jan 23, 2014
Citations: 11	License type: CC BY 2.0

Affiliation: University of Southampton

Abstract

In the October 2013 issue of Acta Neuropathologica there were three very interesting articles on: Amyloid or tau: the chicken or the egg? In the first article, David Mann and John Hardy argued that the deposition of aggregated amyloid β (Aβ) protein in the brain is a primary driving force behind the pathogenesis of Alzheimer’s disease with tau pathology following as a consequential or at least a secondary event. In the communication that followed, Braak and Del Tredici presented the contrary argument with accumulation of tau protein as the primary event in sporadic Alzheimer’s disease. Attems and Jellinger questioned the concept of a chicken and egg and suggested that the majority of cases of age-associated dementia are not caused by one single primary pathological mechanism.

Highlights

Many of the arguments put forward in these three contributions rely on observations derived from human brain material
Have we identified the egg? What is the primary problem? In order to answer this question we should perhaps review the changes that occur in the brain with age and how they affect the pathophysiology of the brain and result in dementia
One example of this approach would be to consider the major risk factors for sporadic Alzheimer’s disease viz: age and possession of the ε4 allele of apolipoprotein E (APOE4), and take the lead from observations in human brains to ask the questions “Why does amyloid β (Aβ) accumulate in the brain with age?” “What are the pathophysiological consequences for the brain of the accumulation of Aβ in the walls of cerebral arteries and in brain parenchyma?” It is clear from the study of human brains that there is an age-related failure of elimination of Aβ

Summary

Introduction

Many of the arguments put forward in these three contributions rely on observations derived from human brain material. One example of this approach would be to consider the major risk factors for sporadic Alzheimer’s disease viz: age and possession of the ε4 allele of apolipoprotein E (APOE4), and take the lead from observations in human brains to ask the questions “Why does Aβ accumulate in the brain with age?” “What are the pathophysiological consequences for the brain of the accumulation of Aβ in the walls of cerebral arteries and in brain parenchyma?” It is clear from the study of human brains that there is an age-related failure of elimination of Aβ.

Results

Conclusion