Development and validation of a novel Simoa assay for NPTX2 in Alzheimer's disease and Down syndrome
(2025) In Alzheimer's and Dementia 21(6).- Abstract
INTRODUCTION: Synaptic dysfunction and loss are pathological hallmarks of neurodegenerative diseases. Neuronal pentraxin 2 (NPTX2), a presynaptic protein involved in synaptic plasticity, has been linked to cognitive decline in Alzheimer's disease (AD) and other neurodegenerative disorders. METHODS: We developed and validated a novel single molecule array (Simoa) for NPTX2 in cerebrospinal fluid, which was evaluated in two independent cohorts. RESULTS: CSF NPTX2 concentration was lower (fold change [FC] 0.82, p < 0.01) in AD patients and Down syndrome individuals (FC 0.56, p < 0.001), compared with cognitively unimpaired patients (CU). It was also associated with Mini-Mental State Examination (MMSE) score (β = 2.51, p < 0.001),... (More)
INTRODUCTION: Synaptic dysfunction and loss are pathological hallmarks of neurodegenerative diseases. Neuronal pentraxin 2 (NPTX2), a presynaptic protein involved in synaptic plasticity, has been linked to cognitive decline in Alzheimer's disease (AD) and other neurodegenerative disorders. METHODS: We developed and validated a novel single molecule array (Simoa) for NPTX2 in cerebrospinal fluid, which was evaluated in two independent cohorts. RESULTS: CSF NPTX2 concentration was lower (fold change [FC] 0.82, p < 0.01) in AD patients and Down syndrome individuals (FC 0.56, p < 0.001), compared with cognitively unimpaired patients (CU). It was also associated with Mini-Mental State Examination (MMSE) score (β = 2.51, p < 0.001), tau-PET (β = −0.21, p < 0.01), and cortical thickness (β = 0.08, p < 0.001). DISCUSSION: We describe the first assay for NPTX2 on the Simoa platform, where we continue to highlight the valuable addition of NPTX2 to routine diagnostics of suspected cognitive impairment in patients as it associates better with cognition than other, more established AD biomarkers. Highlights: Novel method validated for measuring CSF NPTX2 on semi-automated Simoa platform. Method validated for use in CSF, where it shows a significant decrease in both AD and DS patients. Associated with cognition, neurofibrillary tangles, and cortical thickness in AD patients. Associations with cognition are shown to be stronger than those of pTau and NFL.
(Less)
- author
- Sauer, Mathias
LU
; Gomes, Bárbara Fernandes
; Shahrouki, Parasto
; Lantero-Rodriguez, Juan
; Montoliu-Gaya, Laia
; Camporesi, Elena
; Belbin, Olivia
; Alcolea, Daniel
; Kumar, Ashish
; Sharma, Mitu
; Singh, Sangeeta
; Brinkmalm, Gunnar
; Gobom, Johan
; Carmona-Iragui, María
; Schöll, Michael
; Janelidze, Shorena
LU
; Deep, Gagan
; Blennow, Kaj
; Zetterberg, Henrik
; Brinkmalm, Ann
; Lleó, Alberto
; Fortea, Juan
; Hansson, Oskar
LU
; Ashton, Nicholas J.
and Nilsson, Johanna
(Less) - organization
- publishing date
- 2025-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, biomarker, cerebrospinal fluid, down syndrome, neuronal pentraxin 2, Simoa, synaptic biomarker
- in
- Alzheimer's and Dementia
- volume
- 21
- issue
- 6
- article number
- e70241
- publisher
- Wiley
- external identifiers
-
- pmid:40522075
- scopus:105008371476
- ISSN
- 1552-5260
- DOI
- 10.1002/alz.70241
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
- id
- df2f1a79-2182-4e62-a1b6-991a2777148f
- date added to LUP
- 2025-12-22 12:59:29
- date last changed
- 2025-12-23 03:00:03
@article{df2f1a79-2182-4e62-a1b6-991a2777148f,
abstract = {{<p>INTRODUCTION: Synaptic dysfunction and loss are pathological hallmarks of neurodegenerative diseases. Neuronal pentraxin 2 (NPTX2), a presynaptic protein involved in synaptic plasticity, has been linked to cognitive decline in Alzheimer's disease (AD) and other neurodegenerative disorders. METHODS: We developed and validated a novel single molecule array (Simoa) for NPTX2 in cerebrospinal fluid, which was evaluated in two independent cohorts. RESULTS: CSF NPTX2 concentration was lower (fold change [FC] 0.82, p < 0.01) in AD patients and Down syndrome individuals (FC 0.56, p < 0.001), compared with cognitively unimpaired patients (CU). It was also associated with Mini-Mental State Examination (MMSE) score (β = 2.51, p < 0.001), tau-PET (β = −0.21, p < 0.01), and cortical thickness (β = 0.08, p < 0.001). DISCUSSION: We describe the first assay for NPTX2 on the Simoa platform, where we continue to highlight the valuable addition of NPTX2 to routine diagnostics of suspected cognitive impairment in patients as it associates better with cognition than other, more established AD biomarkers. Highlights: Novel method validated for measuring CSF NPTX2 on semi-automated Simoa platform. Method validated for use in CSF, where it shows a significant decrease in both AD and DS patients. Associated with cognition, neurofibrillary tangles, and cortical thickness in AD patients. Associations with cognition are shown to be stronger than those of pTau and NFL.</p>}},
author = {{Sauer, Mathias and Gomes, Bárbara Fernandes and Shahrouki, Parasto and Lantero-Rodriguez, Juan and Montoliu-Gaya, Laia and Camporesi, Elena and Belbin, Olivia and Alcolea, Daniel and Kumar, Ashish and Sharma, Mitu and Singh, Sangeeta and Brinkmalm, Gunnar and Gobom, Johan and Carmona-Iragui, María and Schöll, Michael and Janelidze, Shorena and Deep, Gagan and Blennow, Kaj and Zetterberg, Henrik and Brinkmalm, Ann and Lleó, Alberto and Fortea, Juan and Hansson, Oskar and Ashton, Nicholas J. and Nilsson, Johanna}},
issn = {{1552-5260}},
keywords = {{Alzheimer's disease; biomarker; cerebrospinal fluid; down syndrome; neuronal pentraxin 2; Simoa; synaptic biomarker}},
language = {{eng}},
number = {{6}},
publisher = {{Wiley}},
series = {{Alzheimer's and Dementia}},
title = {{Development and validation of a novel Simoa assay for NPTX2 in Alzheimer's disease and Down syndrome}},
url = {{http://dx.doi.org/10.1002/alz.70241}},
doi = {{10.1002/alz.70241}},
volume = {{21}},
year = {{2025}},
}