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Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD
Our understanding of the pathogenesis of Alzheimer disease (AD) has been greatly influenced by investigation of rare families with autosomal dominant mutations that cause early onset AD. Mutations in the genes coding for amyloid precursor protein (APP), presenilin 1 (PSEN-1), and presenilin 2 (PSEN-...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483518/ https://www.ncbi.nlm.nih.gov/pubmed/26175713 http://dx.doi.org/10.3389/fneur.2015.00142 |
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author | Schindler, Suzanne Elizabeth Fagan, Anne M. |
author_facet | Schindler, Suzanne Elizabeth Fagan, Anne M. |
author_sort | Schindler, Suzanne Elizabeth |
collection | PubMed |
description | Our understanding of the pathogenesis of Alzheimer disease (AD) has been greatly influenced by investigation of rare families with autosomal dominant mutations that cause early onset AD. Mutations in the genes coding for amyloid precursor protein (APP), presenilin 1 (PSEN-1), and presenilin 2 (PSEN-2) cause over-production of the amyloid-β peptide (Aβ) leading to early deposition of Aβ in the brain, which in turn is hypothesized to initiate a cascade of processes, resulting in neuronal death, cognitive decline, and eventual dementia. Studies of cerebrospinal fluid (CSF) from individuals with the common form of AD, late-onset AD (LOAD), have revealed that low CSF Aβ42 and high CSF tau are associated with AD brain pathology. Herein, we review the literature on CSF biomarkers in autosomal dominant AD (ADAD), which has contributed to a detailed road map of AD pathogenesis, especially during the preclinical period, prior to the appearance of any cognitive symptoms. Current drug trials are also taking advantage of the unique characteristics of ADAD and utilizing CSF biomarkers to accelerate development of effective therapies for AD. |
format | Online Article Text |
id | pubmed-4483518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44835182015-07-14 Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD Schindler, Suzanne Elizabeth Fagan, Anne M. Front Neurol Neuroscience Our understanding of the pathogenesis of Alzheimer disease (AD) has been greatly influenced by investigation of rare families with autosomal dominant mutations that cause early onset AD. Mutations in the genes coding for amyloid precursor protein (APP), presenilin 1 (PSEN-1), and presenilin 2 (PSEN-2) cause over-production of the amyloid-β peptide (Aβ) leading to early deposition of Aβ in the brain, which in turn is hypothesized to initiate a cascade of processes, resulting in neuronal death, cognitive decline, and eventual dementia. Studies of cerebrospinal fluid (CSF) from individuals with the common form of AD, late-onset AD (LOAD), have revealed that low CSF Aβ42 and high CSF tau are associated with AD brain pathology. Herein, we review the literature on CSF biomarkers in autosomal dominant AD (ADAD), which has contributed to a detailed road map of AD pathogenesis, especially during the preclinical period, prior to the appearance of any cognitive symptoms. Current drug trials are also taking advantage of the unique characteristics of ADAD and utilizing CSF biomarkers to accelerate development of effective therapies for AD. Frontiers Media S.A. 2015-06-29 /pmc/articles/PMC4483518/ /pubmed/26175713 http://dx.doi.org/10.3389/fneur.2015.00142 Text en Copyright © 2015 Schindler and Fagan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Schindler, Suzanne Elizabeth Fagan, Anne M. Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD |
title | Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD |
title_full | Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD |
title_fullStr | Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD |
title_full_unstemmed | Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD |
title_short | Autosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD |
title_sort | autosomal dominant alzheimer disease: a unique resource to study csf biomarker changes in preclinical ad |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483518/ https://www.ncbi.nlm.nih.gov/pubmed/26175713 http://dx.doi.org/10.3389/fneur.2015.00142 |
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