Cited by 106Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

Imaging and cerebrospinal fluid biomarkers in early preclinical alzheimer disease

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Vlassenko, Andrei G., McCue, Lena, Jasielec, Mateusz S., Su, Yi, Gordon, Brian A., Xiong, Chengjie, Holtzman, David M., Benzinger, Tammie L. S. +2 more·2016·Annals of Neurology

Abstract

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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  1. [22]Mintun MA Larossa GN Sheline YI [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease Neurology 2006 8 8 67 3 446 52 16894106

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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.
Venue
Annals of Neurology
Publisher
Wiley
Published
2016-07-25
Volume
80
Issue
3
Pages
379-387
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
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
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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