Journal Article DZNE-2026-00390

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Plasma GFAP outperforms CSF GFAP in detecting amyloid pathology and is associated with increased risk of clinical progression in early Alzheimer's disease.

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2026
Elsevier Masson SAS [Paris]

The journal of prevention of Alzheimer's disease 13(5), 100544 () [10.1016/j.tjpad.2026.100544]

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Abstract: Early and accurate detection of Alzheimer's disease (AD) is essential for timely intervention and development of disease-modifying treatments. The DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) provides a deeply phenotyped cohort covering preclinical and early clinical stages, including subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Astrocyte reactivity and its biomarkers, particularly glial fibrillary acidic protein (GFAP), have gained increasing attention in AD research; however, the relationship between GFAP and amyloid in early disease, as well as its potential prognostic value beyond its association with amyloid status, remains insufficiently understood.To evaluate the performance of CSF and plasma GFAP across early disease stages, compare these measures according to amyloid status, and assess the prognostic value of GFAP for clinical progression across diagnostic stages during longitudinal follow-up.This study used data from the multicenter DELCODE cohort in Germany, including participants with available plasma and/or CSF samples and standardized clinical, cognitive, imaging, and biomarker assessments.GFAP concentrations in plasma and CSF were quantified using validated immunoassay platforms. Standard CSF AD biomarkers and ApoE genotype were measured using established assays. Amyloid status was defined by the CSF Aβ42/40 ratio. Longitudinal follow-up occurred annually for up to ∼10 years, with clinical conversion determined according to NIA-AA criteria.Plasma and CSF GFAP increased across the AD continuum, with higher levels in MCI and AD (p < 0.001). Plasma GFAP showed a stronger association with amyloid status than CSF GFAP across all groups. In MCI, plasma GFAP combined with age and ApoE4 yielded an AUC of 0.87. Elevated plasma GFAP predicted increased risk of conversion to MCI (HR = 2.19, p < 0.001; adjusted HR = 1.70, p = 0.0056) and AD dementia (HR = 3.5; adjusted HR = 2.49 both p < 0.001).Plasma GFAP is a sensitive, minimally invasive biomarker with diagnostic relevance for amyloid detection and prognostic relevance for clinical progression in early AD.

Keyword(s): Alzheimer’s disease ; Blood biomarkers of Alzheimer’s disease ; Cerebrospinal fluid (CSF) ; Glial fibrillary acidic protein (GFAP) ; Mild cognitive impairment ; Subjective memory decline

Classification:

Contributing Institute(s):
  1. Biomarker-Assisted Early Detection of Dementias (AG Peters)
  2. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
  3. Translational Dementia Research (Bonn) (AG Schneider)
  4. Patient Studies (Bonn) (Patient Studies (Bonn))
  5. Clinical Research (Munich) (Clinical Research (Munich))
  6. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
  7. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
  8. Parkinson Genetics (AG Gasser)
  9. Core ICRU (ICRU)
  10. Neuropsychology (AG Wagner)
  11. Neuroinflammation, Biomarker (AG Heneka)
  12. Translational Neuropsychiatry (AG Priller)
  13. Clinical Neurophysiology and Memory (AG Düzel)
  14. Clinical Alzheimer’s Disease Research (AG Jessen)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Database coverage:
Medline ; DOAJ ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; DEAL Springer ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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The record appears in these collections:
Institute Collections > M DZNE > M DZNE-Clinical Research (Munich)
Institute Collections > BN DZNE > BN DZNE-Patient Studies (Bonn)
Document types > Articles > Journal Article
Institute Collections > GÖ DZNE > GÖ DZNE-AG Wiltfang
Institute Collections > BN DZNE > BN DZNE-AG Schneider
Institute Collections > ROS DZNE > ROS DZNE-AG Teipel
Institute Collections > TÜ DZNE > TÜ DZNE-AG Gasser
Institute Collections > BN DZNE > BN DZNE-AG Jessen
Institute Collections > MD DZNE > MD DZNE-AG Düzel
Institute Collections > BN DZNE > BN DZNE-AG Wagner
Institute Collections > BN DZNE > BN DZNE-AG Heneka
Institute Collections > M DZNE > M DZNE-AG Dichgans
Institute Collections > B DZNE > B DZNE-AG Priller
Institute Collections > B DZNE > B DZNE-AG Peters
Institute Collections > TÜ DZNE > TÜ DZNE-ICRU
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 Record created 2026-04-13, last modified 2026-04-13


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