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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Julie Lee1, Balazs Toth1, Sandra Sanabria Bohorquez1

  • 1Genentech, Inc., South San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Researchers identified a specific tau peptide in cerebrospinal fluid (CSF) that strongly correlates with Alzheimer's Disease (AD) brain pathology. This finding offers a promising, accessible biomarker for assessing tau tangles in AD clinical trials.

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Area of Science:

  • Neuroscience
  • Biomarker Discovery
  • Alzheimer's Disease Research

Background:

  • Neurofibrillary tangles (NFTs), composed of aggregated tau protein, are key pathological markers of Alzheimer's Disease (AD).
  • Tau is a critical biomarker in AD clinical trials for diagnosis, prognosis, and assessing treatment efficacy.
  • Current tau imaging via PET scans is limited by cost and infrastructure requirements.

Purpose of the Study:

  • To investigate the correlation between specific cerebrospinal fluid (CSF) soluble tau species and in vivo tau PET imaging.
  • To identify accessible fluid biomarkers as alternatives to PET imaging for assessing tau pathology in AD clinical trials.

Main Methods:

  • Measured CSF tau species (total tau, pTau181, pTau205, N-term, Mid-domain, pTau217, and proteomic peptides) using DIA-MS, Elecsys, LC-MS, and Simoa assays in 53 AD participants.
  • Correlated CSF tau measurements with [18F]GTP1 PET imaging (SUVR) in cortical and meta-temporal regions.
  • Validated correlations in 46 post-mortem AD brains by comparing CSF tau peptides with AT8-positive NFT burden in the fusiform gyrus.

Main Results:

  • CSF pTau205, pTau217, and a proteomic peptide from the 2N4R isoform MTBR region showed the highest correlation with [18F]GTP1 SUVR.
  • The MTBR peptide demonstrated a strong correlation with the percentage of AT8-positive area in the fusiform gyrus, indicating brain NFT burden.

Conclusions:

  • A proteomic peptide from the MTBR region of tau was identified as the most highly correlated tau species in AD CSF with both in vivo tau PET imaging and ex vivo brain pathology.
  • This MTBR peptide represents a potential fluid biomarker for assessing tau pathology in AD, offering a more accessible alternative to PET imaging in clinical trials.