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Biological subtypes of Alzheimer disease: A systematic review and meta-analysis

OBJECTIVE: To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data. METHODS: EMBASE, PubMed, and Web of Science databases...

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Autores principales: Ferreira, Daniel, Nordberg, Agneta, Westman, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238917/
https://www.ncbi.nlm.nih.gov/pubmed/32047067
http://dx.doi.org/10.1212/WNL.0000000000009058
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author Ferreira, Daniel
Nordberg, Agneta
Westman, Eric
author_facet Ferreira, Daniel
Nordberg, Agneta
Westman, Eric
author_sort Ferreira, Daniel
collection PubMed
description OBJECTIVE: To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data. METHODS: EMBASE, PubMed, and Web of Science databases were consulted until July 2019. RESULTS: Neuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE ε4 genotype, and CSF biomarker levels. CONCLUSION: We identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD.
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spelling pubmed-72389172020-06-15 Biological subtypes of Alzheimer disease: A systematic review and meta-analysis Ferreira, Daniel Nordberg, Agneta Westman, Eric Neurology Views & Reviews OBJECTIVE: To test the hypothesis that distinct subtypes of Alzheimer disease (AD) exist and underlie the heterogeneity within AD, we conducted a systematic review and meta-analysis on AD subtype studies based on postmortem and neuroimaging data. METHODS: EMBASE, PubMed, and Web of Science databases were consulted until July 2019. RESULTS: Neuropathology and neuroimaging studies have consistently identified 3 subtypes of AD based on the distribution of tau-related pathology and regional brain atrophy: typical, limbic-predominant, and hippocampal-sparing AD. A fourth subtype, minimal atrophy AD, has been identified in several neuroimaging studies. Typical AD displays tau-related pathology and atrophy both in hippocampus and association cortex and has a pooled frequency of 55%. Limbic-predominant, hippocampal-sparing, and minimal atrophy AD had a pooled frequency of 21%, 17%, and 15%, respectively. Between-subtype differences were found in age at onset, age at assessment, sex distribution, years of education, global cognitive status, disease duration, APOE ε4 genotype, and CSF biomarker levels. CONCLUSION: We identified 2 core dimensions of heterogeneity: typicality and severity. We propose that these 2 dimensions determine individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies. This model is envisioned to aid with framing hypotheses, study design, interpretation of results, and understanding mechanisms in future subtype studies. Our model can be used along the A/T/N classification scheme for AD biomarkers. Unraveling the heterogeneity within AD is critical for implementing precision medicine approaches and for ultimately developing successful disease-modifying drugs for AD. Lippincott Williams & Wilkins 2020-03-10 /pmc/articles/PMC7238917/ /pubmed/32047067 http://dx.doi.org/10.1212/WNL.0000000000009058 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Views & Reviews
Ferreira, Daniel
Nordberg, Agneta
Westman, Eric
Biological subtypes of Alzheimer disease: A systematic review and meta-analysis
title Biological subtypes of Alzheimer disease: A systematic review and meta-analysis
title_full Biological subtypes of Alzheimer disease: A systematic review and meta-analysis
title_fullStr Biological subtypes of Alzheimer disease: A systematic review and meta-analysis
title_full_unstemmed Biological subtypes of Alzheimer disease: A systematic review and meta-analysis
title_short Biological subtypes of Alzheimer disease: A systematic review and meta-analysis
title_sort biological subtypes of alzheimer disease: a systematic review and meta-analysis
topic Views & Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238917/
https://www.ncbi.nlm.nih.gov/pubmed/32047067
http://dx.doi.org/10.1212/WNL.0000000000009058
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