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Alzheimer's Imaging Consortium.

Luiza Santos Machado1, Guilherme Povala2, Ilaria Pola3

  • 1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, VG, Sweden.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
PubMed
Summary
This summary is machine-generated.

New astrocyte biomarkers, GPC5, LRIG1, and NCAN, are identified in Alzheimer's disease (AD) cerebrospinal fluid (CSF). These biomarkers correlate with amyloid pathology and cognitive status, offering potential for improved AD diagnostics.

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Area of Science:

  • Neuroscience
  • Biomarker Discovery
  • Alzheimer's Disease Research

Background:

  • Astrocytes play a critical role in Alzheimer's disease (AD) pathophysiology.
  • Glial fibrillary acidic protein (GFAP) is a known biomarker for astrocyte reactivity in AD but doesn't fully capture disease dynamics.
  • There is a need for novel cerebrospinal fluid (CSF) astrocyte biomarkers to better understand AD-related pathological changes.

Purpose of the Study:

  • To identify novel astrocyte-specific biomarkers in CSF for Alzheimer's disease.
  • To investigate the association of these biomarkers with cognitive status and amyloid pathology.

Main Methods:

  • Analysis of CSF proteomic data from 728 individuals in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
  • Examination of CSF protein levels (including GFAP, GPC5, LRIG1, NCAN) across cognitively unimpaired, mild cognitive impairment, and AD groups.
  • Assessment of associations between CSF protein levels and amyloid-beta (Aβ) deposition using [18F]Florbetapir-PET imaging.

Main Results:

  • CSF NCAN levels were significantly reduced in AD individuals compared to cognitively unimpaired (CU) and mild cognitive impairment (MCI) groups.
  • CSF GPC5 levels were elevated in amyloid-beta-positive cognitively impaired individuals.
  • CSF GPC5, LRIG1, and NCAN showed positive associations with Aβ deposition, with GPC5 demonstrating the most widespread cortical associations.

Conclusions:

  • GPC5, LRIG1, and NCAN are identified as novel CSF astrocyte biomarkers that are altered in Alzheimer's disease.
  • GPC5 exhibits a strong association with amyloid deposition, suggesting its potential as a sensitive biomarker for AD.
  • These findings highlight the potential of GPC5 as a novel astrocytic biomarker for AD, with further validation planned.