Decreased cerebrospinal fluid neuronal pentraxin receptor is associated with PET-Aβ load and cerebrospinal fluid Aβ in a pilot study of Alzheimer’s disease
Open accessAbstract
Multifactorial pathological processes of Alzheimer's disease (AD) begin decades prior to clinical onset. Early identification of patients at risk of developing AD using biomarkers reflecting various aspects of pathogenesis is necessary for prevention and early intervention. Cortical β-amyloid (Aβ) burden assessed by positron emission tomography (PET) or cerebrospinal fluid (CSF) levels of Aβ42 are validated biomarkers for early identification. Recently, alterations in levels of neuronal proteins, neuronal pentraxin receptor (NPTXR) and neurofilament light (NfL), in the CSF have emerged as promising AD biomarkers. However, their association with Aβ deposition is not well understood. In this pilot study, we evaluate whether CSF NfL and NPTXR are associated with PET-Aβ imaging and core CSF biomarkers (Aβ42, T-tau, and P-tau). CSF samples were collected from a sub-cohort of participants from the Australian Imaging Biomarkers and Lifestyle study of aging (AIBL) and categorized as either PET-Aβ positive (n = 15) or negative (n = 15). NPTXR was significantly lower in PET-Aβ positive than negative individuals (p = 0.04), and correlated with Aβ42 (rho = 0.69, p < 0.0001), T-tau (rho = 0.45, p = 0.01), and P-tau (rho = 0.51, p = 0.004). However, CSF NfL was not significantly different between PET-Aβ positive and negative individuals and did not correlate with any of the core CSF biomarkers. Similar associations of NPTXR and the core CSF biomarkers persisted in the cognitively normal individuals. Together, NPTXR concentration in CSF may be more sensitive NfL to identify AD risk during the preclinical stage, warranting further investigation into its contribution to AD pathogenesis.
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Both NPTX2 and NPTXR correlated positively with MMSE scores, indicating a possible association with cognitive decline.
“Both NPTX2 and NPTXR correlated positively with MMSE scores, as has been previously shown by other groups [69, 70], indicating a possible association with cognitive decline.”
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- Authors
- Lim, B., Fowler, C., Li, Q.-X., Rowe, C., Dhiman, K., Gupta, V. B., Masters, C. L., Doecke, J. D., Martins, R. N., Collins, S., & Diamandis, E. P.
- Affiliations
- University of Toronto (CA)
- The University of Melbourne (AU)
- Edith Cowan University (AU)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Mount Sinai Hospital (CA)
- Corresponding author
- Diamandis, Eleftherios P.
- ORCID
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 731
- Pages
- 135078
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W3028203785
- Cited by
- 10
- References
- 45
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Research Online (Edith Cowan University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, neurofilament light chain, cerebrospinal fluid biomarkers, amyloid-beta 42, tau protein, preclinical Alzheimer's disease, early detection of Alzheimer's disease, cognitively normal older adults
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Middle Aged, Peptide Fragments, Receptors, Cell Surface, Biomarkers, Amyloid beta-Peptides, tau Proteins, Cognitive Dysfunction
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