Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease
Open accessAbstract
Objective: Deposition of amyloid β (Aβ)‐containing plaques as evidenced by amyloid imaging and cerebrospinal fluid (CSF) Aβ1–42 (Aβ42) is an early indicator of preclinical Alzheimer disease (AD). To better understand their relationship during the earliest preclinical stages, we investigated baseline CSF markers in cognitively normal individuals at different stages of amyloid deposition defined by longitudinal amyloid imaging with Pittsburgh compound B (PIB): (1) PIB‐negative at baseline and follow‐up (PIB − ; normal), (2) PIB‐negative at baseline but PIB‐positive at follow‐up (PIB converters; early preclinical AD), and (3) PIB‐positive at baseline and follow‐up (PIB + ; preclinical AD). Methods: Cognitively normal individuals (n = 164) who had undergone baseline PIB scan and CSF collection within 1 year of each other and at least 1 additional PIB follow‐up were included. Amyloid status was defined dichotomously using an a priori mean cortical cutoff. Results: PIB converters (n = 20) at baseline exhibited significantly lower CSF Aβ42 compared to those who remained PIB‐negative (n = 123), but higher compared to the PIB + group (n = 21). A robust negative correlation ( r = −0.879, p = 0.0001) between CSF Aβ42 and absolute (but subthreshold) PIB binding was observed during this early preclinical stage. The negative correlation was not as strong once individuals were PIB‐positive ( r = −0.456, p = 0.038), and there was no correlation in the stable PIB − group ( p = 0.905) or in the group (n = 10) with early symptomatic AD ( p = 0.537). Interpretation: CSF Aβ42 levels are tightly coupled with cortical amyloid load in the earliest stages of preclinical AD, and begin to decrease dramatically prior to the point when an abnormal threshold of cortical accumulation is detected with amyloid imaging. Ann Neurol 2016;80:379–387
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The L-shaped relationship between CSF Aβ42 and amyloid PET may be due to a temporal offset between these two measures.
“This may be due to a temporal offset between these two measures [121–123].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [123]
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- Authors
- Vlassenko, A. G., McCue, L., Jasielec, M. S., Su, Y., Gordon, B. A., Xiong, C., Holtzman, D. M., Benzinger, T. L. S., Morris, J. C., & Fagan, A. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Vlassenko, Andrei G.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2016-07-25
- Volume
- 80
- Issue
- 3
- Pages
- 379-387
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC5016232
- OpenAlex
- W2492380270
- Cited by
- 106
- References
- 35
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 7 · 2023: 4 · 2022: 14 · 2021: 12 · 2020: 9 · 2019: 16 · 2018: 15 · 2017: 12 · 2016: 3
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P50 AG05681, P01 AG026276, P01 AG03991)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- preclinical Alzheimer's disease, amyloid-beta 42, cerebrospinal fluid biomarkers, amyloid imaging, Pittsburgh compound B, amyloid plaques, cognitively normal individuals, amyloid PET
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Female, Follow-Up Studies, Humans, Male, Middle Aged, Peptide Fragments, Thiazoles, Amyloid beta-Peptides, Disease Progression, Early Diagnosis, Prodromal Symptoms
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