CSF pTDP-43 across the Alzheimer's spectrum: Links to amyloid, APOE and vasculopathy
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View abstract on PubMed
Summary
This summary is machine-generated.Cerebrospinal fluid phosphorylated TDP-43 (pTDP-43) levels do not differentiate between Alzheimer
Area Of Science
- Neuroscience
- Neurology
- Biochemistry
Background
- Accumulation of phosphorylated TDP-43 (pTDP-43) is implicated in Alzheimer's disease (AD) and vascular dementia (VaD).
- Previous research linked perivascular pTDP-43 inclusions to compromised vascular integrity.
- The interplay between pTDP-43, amyloid beta (Aβ), and cerebrovascular pathology requires further investigation.
Purpose Of The Study
- To analyze cerebrospinal fluid (CSF) pTDP-43 levels in individuals with mild cognitive impairment (MCI), AD, and VaD.
- To explore correlations between CSF pTDP-43 and biomarkers of Aβ pathology, vascular integrity, and blood-brain barrier permeability.
- To assess the relationship between CSF pTDP-43 and hippocampal pTDP-43 load.
Main Methods
- CSF pTDP-43 levels were measured using an in-house ELISA in non-demented controls (NC), stable MCI (sMCI), MCI-AD, AD, and VaD.
- Correlations were analyzed between CSF pTDP-43 and established biomarkers for Aβ pathology, vascular integrity, and BBB permeability.
- pTDP-43 levels in postmortem CSF and hippocampal pTDP-43 load were also analyzed.
Main Results
- CSF pTDP-43 levels did not significantly differ across diagnostic groups or APOE genotypes.
- CSF pTDP-43 showed correlations with Aβ markers in sMCI and VaD groups.
- CSF pTDP-43 levels trended towards a negative correlation with hippocampal pTDP-43 load.
Conclusions
- CSF pTDP-43, as measured by ELISA, cannot reliably distinguish between MCI, AD, and VaD.
- CSF pTDP-43 may serve as an indicator of hippocampal pTDP-43 burden.
- CSF pTDP-43 is associated with certain vascular and Aβ-related changes in specific patient groups.
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