The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology
The definitive diagnosis of Alzheimer’s disease (AD) rests with post-mortem neuropathology despite the advent of more sensitive scanning and the search for reliable biomarkers. Even though the classic neuropathological features of AD have been known for many years, it was only relatively recently th...
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doaj-fce7a37ee09c46bdb832cc62b858fbb82020-11-25T02:50:09ZengMDPI AGBrain Sciences2076-34252020-07-011047947910.3390/brainsci10080479The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant PathologyAndrew King0Istvan Bodi1Claire Troakes2Department of Clinical Neuropathology, King’s College Hospital, Denmark Hill, London SE5 9RS, UKDepartment of Clinical Neuropathology, King’s College Hospital, Denmark Hill, London SE5 9RS, UKLondon Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Psychology & Neuroscience, King’s College, London SE5 8AF, UKThe definitive diagnosis of Alzheimer’s disease (AD) rests with post-mortem neuropathology despite the advent of more sensitive scanning and the search for reliable biomarkers. Even though the classic neuropathological features of AD have been known for many years, it was only relatively recently that more sensitive immunohistochemistry for amyloid beta (Aβ) and hyperphosphorylated tau (HP-tau) replaced silver-staining techniques. However, immunohistochemistry against these and other proteins has not only allowed a more scientific evaluation of the pathology of AD but also revealed some mimics of HP-tau pathological patterns of AD, including age-related changes, argyrophilic grain disease and chronic traumatic encephalopathy. It also highlighted a number of cases of AD with significant additional pathology including Lewy bodies, phosphorylated TDP-43 (p-TDP-43) positive neuronal cytoplasmic inclusions and vascular pathology. This concomitant pathology can cause a number of challenges including the evaluation of the significance of each pathological entity in the make-up of the clinical symptoms, and the threshold of each individual pathology to cause dementia. It also raises the possibility of underlying common aetiologies. Furthermore, the concomitant pathologies could provide explanations as to the relative failure of clinical trials of anti-Aβ therapy in AD patients.https://www.mdpi.com/2076-3425/10/8/479Alzheimer’sdementiaTDP-43Lewyvasculartauopathies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrew King Istvan Bodi Claire Troakes |
spellingShingle |
Andrew King Istvan Bodi Claire Troakes The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology Brain Sciences Alzheimer’s dementia TDP-43 Lewy vascular tauopathies |
author_facet |
Andrew King Istvan Bodi Claire Troakes |
author_sort |
Andrew King |
title |
The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology |
title_short |
The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology |
title_full |
The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology |
title_fullStr |
The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology |
title_full_unstemmed |
The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology |
title_sort |
neuropathological diagnosis of alzheimer’s disease—the challenges of pathological mimics and concomitant pathology |
publisher |
MDPI AG |
series |
Brain Sciences |
issn |
2076-3425 |
publishDate |
2020-07-01 |
description |
The definitive diagnosis of Alzheimer’s disease (AD) rests with post-mortem neuropathology despite the advent of more sensitive scanning and the search for reliable biomarkers. Even though the classic neuropathological features of AD have been known for many years, it was only relatively recently that more sensitive immunohistochemistry for amyloid beta (Aβ) and hyperphosphorylated tau (HP-tau) replaced silver-staining techniques. However, immunohistochemistry against these and other proteins has not only allowed a more scientific evaluation of the pathology of AD but also revealed some mimics of HP-tau pathological patterns of AD, including age-related changes, argyrophilic grain disease and chronic traumatic encephalopathy. It also highlighted a number of cases of AD with significant additional pathology including Lewy bodies, phosphorylated TDP-43 (p-TDP-43) positive neuronal cytoplasmic inclusions and vascular pathology. This concomitant pathology can cause a number of challenges including the evaluation of the significance of each pathological entity in the make-up of the clinical symptoms, and the threshold of each individual pathology to cause dementia. It also raises the possibility of underlying common aetiologies. Furthermore, the concomitant pathologies could provide explanations as to the relative failure of clinical trials of anti-Aβ therapy in AD patients. |
topic |
Alzheimer’s dementia TDP-43 Lewy vascular tauopathies |
url |
https://www.mdpi.com/2076-3425/10/8/479 |
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