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. 2024 Feb 23;16(1):e12556.
doi: 10.1002/dad2.12556. eCollection 2024 Jan-Mar.

Association of CSF biomarkers with MRI brain changes in Alzheimer's disease

Nazib M Seidu  1 , Silke Kern  1   2 , Simona Sacuiu  1   2   3   4 , Therese Rydberg Sterner  1   5 , Kaj Blennow  6   7 , Henrik Zetterberg  6   7   8   9   10   11 , Olof Lindberg  3 , Daniel Ferreira  3   12 , Eric Westman  3   13 , Anna Zettergren  1 , Ingmar Skoog  1   2
Affiliations

Association of CSF biomarkers with MRI brain changes in Alzheimer's disease

Nazib M Seidu et al. Alzheimers Dement (Amst). .

Abstract

The relation between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and magnetic resonance imaging (MRI) measures is poorly understood in cognitively healthy individuals from the general population. Participants' (n = 226) mean age was 70.9 years (SD = 0.4). CSF concentrations of amyloid beta (Aβ)1-42, total tau (t-tau), phosphorylated tau (p-tau), neurogranin, and neurofilament light, and volumes of hippocampus, amygdala, total basal forebrain (TBF), and cortical thickness were measured. Linear associations between CSF biomarkers and MRI measures were investigated. In Aβ1-42 positives, higher t-tau and p-tau were associated with smaller hippocampus (P = 0.001 and P = 0.003) and amygdala (P = 0.005 and P = 0.01). In Aβ1-42 negatives, higher t-tau, p-tau, and neurogranin were associated with larger TBF volume (P = 0.001, P = 0.001, and P = 0.01). No associations were observed between the CSF biomarkers and an AD signature score of cortical thickness. AD-specific biomarkers in cognitively healthy 70-year-olds may be related to TBF, hippocampus, and amygdala. Lack of association with cortical thickness might be due to early stage of disease.

Keywords: Alzheimer's disease; amygdala; amyloid beta 1‐42; cerebrospinal fluid biomarkers; cognitively healthy; cortical Alzheimer's disease signature score; hippocampus; magnetic resonance imaging measures; neurofilament light protein; neurogranin; phosphorylated tau; total basal forebrain; total tau.

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Conflict of interest statement

KB has served as a consultant, on advisory boards, or data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Roche Diagnostics, and Siemens Healthineers, and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. HZ has served on scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Passage Bio, Pinteon Therapeutics, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). SK has served on scientific advisory boards and/or as a consultant for Geras Solutions, Optoceutics, and Biogen, unrelated to the present study. The authors declare no conflicts of interest. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Relations between CSF Aβ42 and MRI measures in the total sample. Gray lines are the correlation lines showing the trends. Aβ, amyloid beta; AD, Alzheimer's disease; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; TBF, total basal forebrain.
FIGURE 2
FIGURE 2
Relations between CSF biomarkers and MRI measures after stratification on Aβ42 pathology. Red dots = Aβ‐positives: ≤ 530 pg/mL. Blue dots = Aβ‐negatives: > 530 pg/mL. Red lines are the correlation lines showing the trends for Aβ‐positives and blue lines are the correlation lines showing the trends for Aβ‐negatives. Aβ, amyloid beta; AD, Alzheimer's disease; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; TBF, total basal forebrain.
FIGURE 3
FIGURE 3
Forest plot of the associations between CSF biomarkers and MRI measures in the total sample (A), and after stratification on Aβ42 pathology, (B) Aβ‐positives: ≤ 530 pg/mL, and (C) Aβ‐negatives: > 530 pg/mL. Aβ, amyloid beta; AD, Alzheimer's disease; CI, confidence interval; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; TBF, total basal forebrain.
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