Biomarker-based staging of Alzheimer disease : rationale and clinical applications
(2024) In Nature Reviews Neurology- Abstract
Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity of Alzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and breakthroughs in molecular imaging have opened up the possibility of in vivo staging of AD. Focusing on the key principles of disease staging shared across several areas of medicine, this Review highlights the potential for in vivo staging of AD to transform our understanding of preclinical AD, refine enrolment criteria for trials of disease-modifying therapies and aid clinical... (More)
Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity of Alzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and breakthroughs in molecular imaging have opened up the possibility of in vivo staging of AD. Focusing on the key principles of disease staging shared across several areas of medicine, this Review highlights the potential for in vivo staging of AD to transform our understanding of preclinical AD, refine enrolment criteria for trials of disease-modifying therapies and aid clinical decision-making in the era of anti-amyloid therapeutics. We provide a state-of-the-art review of recent biomarker-based AD staging systems and highlight their contributions to the understanding of the natural history of AD. Furthermore, we outline hypothetical frameworks to stage AD severity using more accessible fluid biomarkers. In addition, by applying amyloid PET-based staging to recently published anti-amyloid therapeutic trials, we highlight how biomarker-based disease staging frameworks could illustrate the numerous pathological changes that have already taken place in individuals with mildly symptomatic AD. Finally, we discuss challenges related to the validation and standardization of disease staging and provide a forward-looking perspective on potential clinical applications.
(Less)
- author
- Therriault, Joseph
; Schindler, Suzanne E.
; Salvadó, Gemma
LU
; Pascoal, Tharick A.
; Benedet, Andréa Lessa
; Ashton, Nicholas J.
; Karikari, Thomas K.
; Apostolova, Liana
; Murray, Melissa E.
; Verberk, Inge
; Vogel, Jacob W.
LU
; La Joie, Renaud
; Gauthier, Serge
; Teunissen, Charlotte
; Rabinovici, Gil D.
; Zetterberg, Henrik
LU
; Bateman, Randall J.
; Scheltens, Philip
; Blennow, Kaj
LU
; Sperling, Reisa
; Hansson, Oskar
LU
; Jack, Clifford R.
and Rosa-Neto, Pedro
(Less) - organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Nature Reviews Neurology
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:38429551
- scopus:85186391264
- ISSN
- 1759-4758
- DOI
- 10.1038/s41582-024-00942-2
- language
- English
- LU publication?
- yes
- id
- 1fc5d241-ddca-404b-bb7e-d0aade1ad325
- date added to LUP
- 2024-03-27 13:04:51
- date last changed
- 2024-04-24 17:04:22
@article{1fc5d241-ddca-404b-bb7e-d0aade1ad325,
abstract = {{<p>Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity of Alzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and breakthroughs in molecular imaging have opened up the possibility of in vivo staging of AD. Focusing on the key principles of disease staging shared across several areas of medicine, this Review highlights the potential for in vivo staging of AD to transform our understanding of preclinical AD, refine enrolment criteria for trials of disease-modifying therapies and aid clinical decision-making in the era of anti-amyloid therapeutics. We provide a state-of-the-art review of recent biomarker-based AD staging systems and highlight their contributions to the understanding of the natural history of AD. Furthermore, we outline hypothetical frameworks to stage AD severity using more accessible fluid biomarkers. In addition, by applying amyloid PET-based staging to recently published anti-amyloid therapeutic trials, we highlight how biomarker-based disease staging frameworks could illustrate the numerous pathological changes that have already taken place in individuals with mildly symptomatic AD. Finally, we discuss challenges related to the validation and standardization of disease staging and provide a forward-looking perspective on potential clinical applications.</p>}},
author = {{Therriault, Joseph and Schindler, Suzanne E. and Salvadó, Gemma and Pascoal, Tharick A. and Benedet, Andréa Lessa and Ashton, Nicholas J. and Karikari, Thomas K. and Apostolova, Liana and Murray, Melissa E. and Verberk, Inge and Vogel, Jacob W. and La Joie, Renaud and Gauthier, Serge and Teunissen, Charlotte and Rabinovici, Gil D. and Zetterberg, Henrik and Bateman, Randall J. and Scheltens, Philip and Blennow, Kaj and Sperling, Reisa and Hansson, Oskar and Jack, Clifford R. and Rosa-Neto, Pedro}},
issn = {{1759-4758}},
language = {{eng}},
publisher = {{Nature Publishing Group}},
series = {{Nature Reviews Neurology}},
title = {{Biomarker-based staging of Alzheimer disease : rationale and clinical applications}},
url = {{http://dx.doi.org/10.1038/s41582-024-00942-2}},
doi = {{10.1038/s41582-024-00942-2}},
year = {{2024}},
}