Preclinical Alzheimer disease—the challenges ahead
Open accessAbstract
There is growing recognition that the pathophysiological process of Alzheimer disease (AD) begins many years prior to clinically obvious symptoms, and the concept of a presymptomatic or preclinical stage of AD is becoming more widely accepted. Advances in biomarker studies have enabled detection of AD pathology in vivo in clinically normal older individuals. The predictive value of these biomarkers at the individual patient level, however, remains to be elucidated. The ultimate goal of identifying individuals in the preclinical stages of AD is to facilitate early intervention to delay and perhaps even prevent emergence of the clinical syndrome. A number of challenges remain to be overcome before this concept can be validated and translated into clinical practice.
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MRI, PET, and CSF assays for amyloid-β and tau can detect these presymptomatic changes.
“These pathological changes can be assessed by magnetic resonance imaging (MRI), positron-emission tomography (PET), and measurement of amyloid-β and tau protein levels in the cerebrospinal fluid (CSF)1–4.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [4]
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“Whether this group of healthy individual showing a more AD-like pattern of atrophy represents preclinical AD (Sperling et al., 2013) is difficult to determine and would require a longer follow-up and additional AD biomarkers.”
BackgroundAn interpretable deep learning framework identifies proteomic drivers of Alzheimer’s disease
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- Authors
- Sperling, R. A., Karlawish, J., & Johnson, K. A.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Pennsylvania (US)
- Harvard University (US)
- Corresponding author
- Sperling, Reisa A.
- Venue
- Nature Reviews Neurology
- Published
- 2012-11-27
- Volume
- 9
- Issue
- 1
- Pages
- 54-58
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC3643203
- OpenAlex
- W1988404208
- Cited by
- 291
- References
- 31
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 20 · 2023: 15 · 2022: 31 · 2021: 17 · 2020: 28 · 2019: 18 · 2018: 27 · 2017: 25 · 2016: 18 · 2015: 15 · 2014: 25 · 2013: 13
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ScholarlyCommons (University of Pennsylvania) (submittedVersion)
- Scholarly Commons (University of Pennsylvania) (submittedVersion)
- Funders
- National Institute on Aging (P30AG010124, R01AG027435, R01AG037497, P50AG005134, P01AG036694)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- preclinical Alzheimer's disease, Alzheimer's disease, biomarkers, early therapeutic intervention, presymptomatic stage, ethical considerations
- MeSH terms
- Aged, Alzheimer Disease, Brain, Genetic Markers, Humans, Risk Factors, Biomarkers, Amyloid beta-Peptides, Disease Progression, Genetic Predisposition to Disease, Early Diagnosis, Apolipoprotein E4, Translational Research, Biomedical, Neuroimaging, Early Medical Intervention
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