NDLI: Plasma S100β is a predictor for pathology and cognitive decline in Alzheimer’s disease

Content Provider	Springer Nature : BioMed Central
Author	Nehra, Geetika Maloney, Bryan J. Smith, Rebecca R. Chumboatong, Wijitra Abner, Erin L. Nelson, Peter T. Bauer, Björn Hartz, Anika M. S.
Abstract	Background Blood–brain barrier dysfunction is one characteristic of Alzheimer’s disease (AD) and is recognized as both a cause and consequence of the pathological cascade leading to cognitive decline. The goal of this study was to assess markers for barrier dysfunction in postmortem tissue samples from research participants who were either cognitively normal individuals (CNI) or diagnosed with AD at the time of autopsy and determine to what extent these markers are associated with AD neuropathologic changes (ADNC) and cognitive impairment. Methods We used postmortem brain tissue and plasma samples from 19 participants: 9 CNI and 10 AD dementia patients who had come to autopsy from the University of Kentucky AD Research Center (UK-ADRC) community-based cohort; all cases with dementia had confirmed severe ADNC. Plasma samples were obtained within 2 years of autopsy. Aβ40, Aβ42, and tau levels in brain tissue samples were quantified by ELISA. Cortical brain sections were cleared using the X-CLARITY™ system and immunostained for neurovascular unit-related proteins. Brain slices were then imaged using confocal microscopy and analyzed for microvascular diameters and immunoreactivity coverage using Fiji/ImageJ. Isolated human brain microvessels were assayed for tight-junction protein expression using the JESS™ automated Western blot system. S100 calcium-binding protein B (S100β), matrix metalloproteinase (MMP)-2, MMP-9, and neuron-specific enolase (NSE) levels in plasma were quantified by ELISA. All outcomes were assessed for linear associations with global cognitive function (MMSE, CDR) and cerebral atrophy scores by Pearson, polyserial, or polychoric correlation, as appropriate, along with generalized linear modeling or generalized linear mixed-level modeling. Results As expected, we detected elevated Aβ and tau pathology in brain tissue sections from AD patients compared to CNI. However, we found no differences in microvascular diameters in cleared AD and CNI brain tissue sections. We also observed no differences in claudin-5 protein levels in capillaries isolated from AD and CNI tissue samples. Plasma biomarker analysis showed that AD patients had 12.4-fold higher S100β plasma levels, twofold lower NSE plasma levels, 2.4-fold higher MMP-9 plasma levels, and 1.2-fold lower MMP-2 plasma levels than CNI. Data analysis revealed that elevated S100β plasma levels were predictive of AD pathology and cognitive impairment. Conclusion Our data suggest that among different markers relevant to barrier dysfunction, plasma S100β is the most promising diagnostic biomarker for ADNC. Further investigation is necessary to assess how plasma S100β levels relate to these changes and whether they may predict clinical outcomes, particularly in the prodromal and early stages of AD.
Related Links	https://fluidsbarrierscns.biomedcentral.com/counter/pdf/10.1186/s12987-024-00615-8.pdf
Ending Page	20
Page Count	20
Starting Page	1
File Format	HTM / HTML
ISSN	20458118
DOI	10.1186/s12987-024-00615-8
Journal	Fluids and Barriers of the CNS
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2025-01-09
Access Restriction	Open
Subject Keyword	Neurosciences Hematology Neurobiology Blood–brain barrier Aβ Tau MMSE
Content Type	Text
Resource Type	Article
Subject	Neurology Developmental Neuroscience Medicine Cellular and Molecular Neuroscience
Journal Impact Factor	5.9/2023
5-Year Journal Impact Factor	7.5/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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