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

Molly Olzinski1, Yann Cobigo2, Rowan Saloner1

  • 1Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
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Summary
This summary is machine-generated.

Lower cerebrospinal fluid (CSF) TMEM106B levels correlate with increased frontotemporal lobar degeneration (FTLD) severity and brain atrophy. CSF TMEM106B may serve as a valuable biomarker for neurodegeneration in FTLD.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biomarker Discovery

Background:

  • TMEM106B is a lysosomal protein and a genetic risk factor for frontotemporal lobar degeneration (FTLD).
  • Aptamer-based proteomics enables quantification of CSF TMEM106B.
  • The clinical utility of CSF TMEM106B as a biomarker for FTLD severity remains unevaluated.

Purpose of the Study:

  • To investigate the association between CSF TMEM106B levels and FTLD disease severity.
  • To explore the relationship between CSF TMEM106B, neurodegeneration, and brain atrophy.
  • To determine the potential of CSF TMEM106B as a clinical biomarker in FTLD.

Main Methods:

  • CSF TMEM106B and NfL protein levels were measured using aptamer-based proteomics in two independent FTLD cohorts (sporadic and familial).
  • Statistical analyses, including linear and mixed linear models, assessed associations between biomarkers and disease severity measures (e.g., CDR®+NACC-FTLD).
  • Voxel-based morphometry analyzed correlations between CSF biomarkers and brain volumes.

Main Results:

  • Lower CSF TMEM106B levels were associated with greater FTLD disease severity, functional decline, cognitive impairment, and depression.
  • Low CSF TMEM106B correlated with reduced brain volumes in frontal, parietal, and temporal regions.
  • CSF NfL showed stronger associations with disease severity, while CSF TMEM106B showed stronger associations with brain volumes.

Conclusions:

  • CSF TMEM106B concentrations are influenced by the rs1990622 genotype and correlate with FTLD disease severity and brain atrophy.
  • Lower CSF TMEM106B levels indicate more severe neurodegeneration and brain volume loss in FTLD.
  • CSF TMEM106B shows potential as a biomarker for neurodegeneration in FTLD, complementing CSF NfL.