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Updated: Aug 14, 2026
Full- versus Sub-Regional Quantification of Amyloid-Beta Load on Mouse Brain Sections
Published on: May 19, 2022
Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans
Anne M Fagan1, Mark A Mintun, Robert H Mach
1Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. fagana@neuro.wustl.edu
Objectives:
Amyloid-beta(42) (Abeta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Abeta(42) is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Abeta(42) "sink," hindering transport of soluble Abeta(42) between brain and CSF. We investigated this hypothesis.
Methods:
We compared the in vivo brain amyloid load (via positron emission tomography imaging of the amyloid-binding agent, Pittsburgh Compound-B [PIB]) with CSF Abeta(42) and other measures (via enzyme-linked immunosorbent assay) in clinically characterized research subjects.
Results:
Subjects fell into two nonoverlapping groups: those with positive PIB binding had the lowest CSF Abeta(42) level, and those with negative PIB binding had the highest CSF Abeta(42) level. No relation was observed between PIB binding and CSF Abeta(40), tau, phospho-tau(181), plasma Abeta(40), or plasma Abeta(42). Importantly, PIB binding and CSF Abeta(42) did not consistently correspond with clinical diagnosis; three cognitively normal subjects were PIB-positive with low CSF Abeta(42), suggesting the presence of amyloid in the absence of cognitive impairment (ie, preclinical AD).
Interpretation:
These observations suggest that brain amyloid deposition results in low CSF Abeta(42), and that amyloid imaging and CSF Abeta(42) may potentially serve as antecedent biomarkers of (preclinical) AD.
Insights
Amyloid plaques in the brain correlate with lower cerebrospinal fluid amyloid-beta(42) levels. This suggests amyloid imaging and CSF Abeta(42) may detect preclinical Alzheimer's disease.
Area of Science:
- Neuroscience
- Biomarkers
- Alzheimer's Disease Research
Background:
- Amyloid-beta(42) (Abeta(42)) is central to Alzheimer's disease (AD) pathogenesis and a major component of amyloid plaques.
- Reduced cerebrospinal fluid (CSF) Abeta(42) levels are observed in Alzheimer's type dementia, potentially due to plaques acting as an Abeta(42) sink.
Purpose of the Study:
- To investigate the hypothesis that brain amyloid deposition leads to decreased CSF Abeta(42) levels.
- To explore the relationship between in vivo brain amyloid load and CSF Abeta(42) in clinically characterized subjects.
Main Methods:
- Compared in vivo brain amyloid load using Pittsburgh Compound-B (PIB) positron emission tomography imaging.
- Measured CSF Abeta(42) and other biomarkers via enzyme-linked immunosorbent assay in research subjects.
Main Results:
- Subjects with positive PIB binding (indicating amyloid plaques) showed the lowest CSF Abeta(42) levels.
- No correlation was found between PIB binding and CSF Abeta(40), tau, phospho-tau(181), or plasma Abeta levels.
- PIB binding and CSF Abeta(42) did not consistently align with clinical diagnosis, with some cognitively normal individuals showing PIB-positive results and low CSF Abeta(42).
Conclusions:
- Brain amyloid deposition appears to cause reduced CSF Abeta(42) levels.
- Amyloid imaging (e.g., PIB) and CSF Abeta(42) may serve as antecedent biomarkers for preclinical Alzheimer's disease.
