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A finger prick collection method for detecting blood biomarkers of neurodegeneration – a pilot study (DROP‐AD)

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AbstractBackgroundPlasma biomarkers have proven to indicate developing cerebral pathologies and injury that underpin neurodegenerative disorders in a non‐invasive manner. However, the measurement of certain blood biomarkers requires on‐site sampling with strict, time‐limited and temperature dependant processing protocols. To further facilitate the usefulness of blood biomarkers, methods for remote and/or unsupervised sample collection would greatly increase the utility as a screening and monitoring tool in secondary care and therapeutic trials.This pilot study investigated a novel method to quantify neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated tau (p‐tau) in capillary dry blood spots (DBScapillary) and venous dry blood spots (DBSvenous).MethodsWe included 77 memory clinic participants from ACE Alzheimer Center Barcelona. DBScapillary, DBSvenous, and EDTA plasma as well as neuropsychological measures were obtained from each participant. A subset (n = 23) had cerebrospinal fluid (CSF) biomarkers. Capillary whole blood was obtained by a macro lancet needle from the left index finger. A total of 65µL of capillary and venous blood were spotted and dried on Noviplex DBS cards, which were shipped overnight without temperature control or cooling to Gothenburg, Sweden. Samples were extracted from DBScapillary and DBSvenous cards, and NfL, GFAP, p‐tau181, and, in a subset (n = 11), p‐tau217 were measured by single molecular array (Simoa). Statistical analysis included Pearson correlation between DBS and EDTA plasma.ResultsDBScapillary GFAP (r = 0.7180, p<0.0001), and NfL (r = 0.6967, p<0.0001) correlated highly with their counterparts in EDTA plasma. We also demonstrated that DBScapillary p‐tau217 (r = 0.8955, p = 0.0002), but not DBScapillary p‐tau181 (r = 0.0132, p = 0.9447) correlated with the same measures in EDTA plasma, likewise DBSvenous GFAP (r = 0.7614, p<0.0001), NfL (r = 0.7701, p<0.0001), p‐tau217 (r = 0.9625, p<0.0001) and p‐tau181 (r = 0.6619, p<0.0001). Moreover, DBScapillary GFAP and DBSvenous GFAP, NfL and p‐tau181 correlated with MMSE, CDR and amyloid status (all p<0.05).ConclusionThis pilot study demonstrates the potential of remote collection and quantification of GFAP, NfL, p‐tau217 and p‐tau181 without low‐temperature storage/transportation or centrifugation (DBSvenous). Our data also suggests that this may be possible from a simple finger prick collection, including p‐tau217. We speculate that this simple, self‐executable method of blood collection would facilitate regular monitoring of patients with suspected neurological conditions.
Title: A finger prick collection method for detecting blood biomarkers of neurodegeneration – a pilot study (DROP‐AD)
Description:
AbstractBackgroundPlasma biomarkers have proven to indicate developing cerebral pathologies and injury that underpin neurodegenerative disorders in a non‐invasive manner.
However, the measurement of certain blood biomarkers requires on‐site sampling with strict, time‐limited and temperature dependant processing protocols.
To further facilitate the usefulness of blood biomarkers, methods for remote and/or unsupervised sample collection would greatly increase the utility as a screening and monitoring tool in secondary care and therapeutic trials.
This pilot study investigated a novel method to quantify neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated tau (p‐tau) in capillary dry blood spots (DBScapillary) and venous dry blood spots (DBSvenous).
MethodsWe included 77 memory clinic participants from ACE Alzheimer Center Barcelona.
DBScapillary, DBSvenous, and EDTA plasma as well as neuropsychological measures were obtained from each participant.
A subset (n = 23) had cerebrospinal fluid (CSF) biomarkers.
Capillary whole blood was obtained by a macro lancet needle from the left index finger.
A total of 65µL of capillary and venous blood were spotted and dried on Noviplex DBS cards, which were shipped overnight without temperature control or cooling to Gothenburg, Sweden.
Samples were extracted from DBScapillary and DBSvenous cards, and NfL, GFAP, p‐tau181, and, in a subset (n = 11), p‐tau217 were measured by single molecular array (Simoa).
Statistical analysis included Pearson correlation between DBS and EDTA plasma.
ResultsDBScapillary GFAP (r = 0.
7180, p<0.
0001), and NfL (r = 0.
6967, p<0.
0001) correlated highly with their counterparts in EDTA plasma.
We also demonstrated that DBScapillary p‐tau217 (r = 0.
8955, p = 0.
0002), but not DBScapillary p‐tau181 (r = 0.
0132, p = 0.
9447) correlated with the same measures in EDTA plasma, likewise DBSvenous GFAP (r = 0.
7614, p<0.
0001), NfL (r = 0.
7701, p<0.
0001), p‐tau217 (r = 0.
9625, p<0.
0001) and p‐tau181 (r = 0.
6619, p<0.
0001).
Moreover, DBScapillary GFAP and DBSvenous GFAP, NfL and p‐tau181 correlated with MMSE, CDR and amyloid status (all p<0.
05).
ConclusionThis pilot study demonstrates the potential of remote collection and quantification of GFAP, NfL, p‐tau217 and p‐tau181 without low‐temperature storage/transportation or centrifugation (DBSvenous).
Our data also suggests that this may be possible from a simple finger prick collection, including p‐tau217.
We speculate that this simple, self‐executable method of blood collection would facilitate regular monitoring of patients with suspected neurological conditions.

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